Skip to main content
SpringerLink
Log in

The early stages of the intracellular transport of membrane proteins: clinical and pharmacological implications

  • Chapter
  • First Online:
Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 151))

Abstract

Intracellular transport mechanisms ensure that integral membrane proteins are delivered to their correct subcellular compartments. Efficient intracellular transport is a prerequisite for the establishment of both cell architecture and function. In the past decade, transport processes of proteins have also drawn the attention of clinicians and pharmacologists since many diseases have been shown to be caused by transport-deficient proteins. Membrane proteins residing within the plasma membrane are transported via the secretory (exocytotic) pathway. The general transport routes of the secretory pathway are well established. The transport of membrane proteins starts with their integration into the ER membrane. The ribosomes synthesizing membrane proteins are targeted to the ER membrane, and the nascent chains are co-translationally integrated into the bilayer, i.e., they are inserted while their synthesis is in progress. During ER insertion, the orientation (topology) of the proteins in the membrane is determined. Proteins are folded, and their folding state is checked by a quality control system that allows only correctly folded forms to leave the ER. Misfolded or incompletely folded forms are retained, transported back to the cytosol and finally subjected to proteolysis. Correctly folded proteins are transported in the membranes of vesicles through the ER/Golgi intermediate compartment (ERGIC) and the individual compartments of the Golgi apparatus (cis, medial, trans) to the plasma membrane. In this review, the current knowledge of the first stages of the intracellular trafficking of membrane proteins will be summarized. This “early secretory pathway” includes the processes of ER insertion, topology determination, folding, quality control and the transport to the Golgi apparatus. Mutations in the genes of membrane proteins frequently lead to misfolded forms that are recognized and retained by the quality control system. Such mutations may cause inherited diseases like cystic fibrosis or retinitis pigmentosa. In the second part of this review, the clinical implications of the early secretory pathway will be discussed. Finally, new pharmacological strategies to rescue misfolded and transport-defective membrane proteins will be outlined.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

AP1:

Clathrin-associated adaptor protein complex 1

AQP:

Aquaporin

ARF:

ADP-ribosylation factor

AVP:

8-Arginine-vasopressin;BiP immunoglobulin heavy chain binding protein

CFTR:

Cystic fibrosis transmembrane conductance regulator

CLQTS:

Congenital long QT syndrome

CMT:

Charcot-Marie-Tooth syndrome

CNX:

Calnexin

COPI:

Coat protein complex I

COPII:

Coat protein complex II

CPX:

8-Cyclopentyl-1,2-dipropylxanthine

CRT:

Calreticulin

CSID:

Congenital sucrose-isomaltase deficiency

Cx:

Connexin

cGMP:

Cyclic 3′:5′ guanosine monophosphate

ECL:

Extracellular loop

EndoH:

Endoglycosidase H

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

ERGIC:

ER/Golgi intermediate compartment

ERp:

ER protein

ETBR:

Human endothelin B receptor

FH:

Familial hypercholesterolemia

GABA:

Gamma amino butyric acid

GFP:

Green fluorescent protein

GH:

Growth hormone

GHIS:

Growth hormone insensitivity syndrome

GLCase:

Glucosidase

GlcNac:

N-acetylglucosamine

GPCR:

G protein-coupled receptor

GPI:

Glycosylphosphatidylinositol

G protein:

GTP-binding protein

GRP:

Glucose-regulated protein

HA:

Hemagglutinin

Hdj-2:

Human DnaJ-2 protein

HFE:

Human hemochromatosis protein

HH:

Hereditary hemochromatosis

HEK 293 cells:

Human embryonic kidney 293 cells

HERG:

Human ether-a-go-go-related protein

Hsc70:

Heat shock cognate 70 protein

ICL:

Intracellular loop

IGF-I:

Insulin-like growth factor-1

IKr :

Rapidly activating delayed rectifier potassium current

IKs :

Slowly activating delayed rectifier potassium current

JAK:

Janus kinase

LDL:

Low-density lipoprotein

LH:

Luteinizing hormone/choriogonadotropin

LS:

Laron syndrome

MATP:

Membrane associated transporter protein

MDCK cells:

Madin-Darby canine kidney epithelial cells

MHC:

Major histocompatibility complex

MiRP1:

minK-related peptide 1

NDI:

Congenital nephrogenic diabetes insipidus

NMDA:

N-methyl-d-aspartate

OCA:

Oculocutaneous albinism

PDI:

Protein disulfide isomerase

Pgp:

P-glycoprotein

PKA:

Protein kinase A

PLP:

Proteolipid protein

PMP22:

Peripheral myelin protein 22

RP:

Primary retinitis pigmentosa

SI:

Sucrase-isomaltase

SNARE:

Ethylmaleimide-sensitive factor attachment protein

SRP:

Signal recognition particle

TCR:

T-cell antigen receptor

TM:

Transmembrane domain

TRAM:

Translocating chain-associated membrane protein

Tyr:

Tyrosinase

Tyrp1:

Tyrosinase-related protein-1

UGGT:

UDP-glucose:glycoprotein glucosyltransferase

VIP:

Vesicular-integral membrane protein

V2R:

Vasopressin V2 receptor

VSV:

Vesicular stomatitis virus

References

  • Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia Cell 97:175–187

    PubMed  CAS  Google Scholar 

  • Akhavan A, Atanasiu R, Shrier A (2003) Identification of a COOH-terminal segment involved in maturation and stability of human ether-a-go-go-related gene potassium channels. J Biol Chem 278:40105–40112

    PubMed  CAS  Google Scholar 

  • Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Dechaux M, Antignac C, Arthus MF, Lonergan M, Turner MS, Balestre MN, Alonso G, Hibert M, Barberis C, Hendy GN, Bichet DG, Jard S (1998) Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 9:1861–1872

    PubMed  CAS  Google Scholar 

  • Amselem S, Duquesnoy P, Attree O, Novelli G, Bousnina S, Postel-Vinay MC, Goossens M (1989) Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 321:989–995

    Article  PubMed  CAS  Google Scholar 

  • Andersen-Beckh B, Dehe M, Sch-lein R, Wiesner B, Rutz C, Liebenhoff U, Rosenthal W, Oksche A (1999) Polarized expression of the vasopressin V2 receptor in Madin-Darby canine kidney cells. Kidney Int. 56:517–527

    PubMed  CAS  Google Scholar 

  • Andersson H, von Heijne G (1994) Membrane protein topology: effects of ΔμH+ on the translocation of charged residues explain the ‘positive inside’ rule. EMBO J 13:2267–2272

    PubMed  CAS  Google Scholar 

  • Andersson H, D’Antona AM, Kendall DA, von Heijne G, Chin CN (2003) Membrane assembly of the cannabinoid receptor 1: impact of a long N-terminal tail. Mol Pharmacol 64:570–577

    PubMed  CAS  Google Scholar 

  • Antonny B, Schekman R (2001) ER export: public transportation by the COPII coach. Curr Opin Cell Biol 13: 438–443

    PubMed  CAS  Google Scholar 

  • Appenzeller C, Andersson H, Kappeler F, Hauri HP (1999) The lectin ERGIC-53 is a cargo transport receptor for glycoproteins. Nat Cell Biol 1:330–334

    PubMed  CAS  Google Scholar 

  • Aridor M, Bannykh SI, Rowe T, Balch WE (1995) Sequential coupling between COPII and COPI vesicle coats in endoplasmic reticulum to Golgi transport. J Cell Biol 131:875–893

    PubMed  CAS  Google Scholar 

  • Aridor M, Hannan-LA (2000) Traffic jam: a compendium of human diseases that affect intracellular transport processes. Traffic 1:836–851

    PubMed  CAS  Google Scholar 

  • Aridor M, Fish KN, Bannykh S, Weissman J, Roberts TH, Lippincott-Schwartz J, Balch WE (2001) the Sar1 GTPase coordinates biosynthetic cargo selection with endoplasmic reticulum export site assembly. J Cell Biol 152: 213–229

    PubMed  CAS  Google Scholar 

  • Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, Sasaki S (2003) Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int 64:2–10

    PubMed  CAS  Google Scholar 

  • Ashcroft FM (2000) Ion channels and disease, Academic Press, San Diego, USA

    Google Scholar 

  • Bannykh SI, Nishimura N, Balch WE (1998) Getting into the Golgi. Trends Cell Biol 8:21–25

    PubMed  CAS  Google Scholar 

  • Bannykh SI, Bannykh GI, Fish KN, Moyer BD, Riordan JR, Balch WE (2000) Traffic pattern of cystic fibrosis transmembrane regulator through the early exocytic pathway. Traffic 1:852–780

    PubMed  CAS  Google Scholar 

  • Beckman LE, Saha N, Spitsyn V, Van Landeghem G, Beckman L (1997) Ethnic differences in the HFE codon 282 (Cys/Tyr) polymorphism. Hum Hered 47:263–267

    PubMed  CAS  Google Scholar 

  • Belden WJ, Barlowe C (2001) Role of Erv29p in collecting soluble secretory proteins into ER-derived transport vesicles. Science 294:1528–1531

    PubMed  CAS  Google Scholar 

  • Bermak JC, Li M, Bullock C, Zhou QY (2001) Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol 3:492–498

    PubMed  CAS  Google Scholar 

  • Bianchi L, Shen Z, Dennis AT, Priori SG, Napolitano C, Ronchetti E, Bryskin R, Schwartz PJ, Brown AM (1999) Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome. Hum Mol Genet 8:1499–1507

    PubMed  CAS  Google Scholar 

  • Bockaert J, Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J 18:1723–1729

    PubMed  CAS  Google Scholar 

  • Bockenhauer D (2001) Ion channels in disease. Curr Opin Pediatr 13:142–149

    PubMed  CAS  Google Scholar 

  • Boissy RE, Zhao H, Oetting WS, Austin LA, Wildenberg SC, Boissy Y, Sturm RA, Hearing VJ, King RA, Nordlund JJ (1996) Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as “OCA3”. Am J Hum Gen 58: 1145–1156

    CAS  Google Scholar 

  • Bone LJ, Deschenes SM, Balice-Gordon RJ, Fischbeck KH, Scherer SS (1997) Connexin32 and X-linked Charcot-Marie-Tooth disease. Neurobiol Dis 4:221–230

    PubMed  CAS  Google Scholar 

  • Borel AC, Simon SM (1996) Biogenesis of polytopic membrane proteins: membrane segments assemble within translocation channels prior to membrane integration. Cell 85:379–389

    PubMed  CAS  Google Scholar 

  • Bonifacino JS, Weissman AM (1998) Ubiquitin and the control of protein fate in the secretory and endocytic pathways. Annu Rev Cell Dev Biol 14:19–57

    PubMed  CAS  Google Scholar 

  • Bradbury NA (1999) Intracellular CFTR: localization and function. Physiol Rev 79:S175–191

    PubMed  CAS  Google Scholar 

  • Brodsky JL (1998) Translocation of proteins across the endoplasmic reticulum membrane. Int Rev Cytol 178: 277–328

    PubMed  CAS  Google Scholar 

  • Brown CR, Hong-Brown LQ, Biwersi J, Verkman AS, Welsh WJ (1996) Chemical chaperones correct the mutant phenotype of the DF508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones 1:117–125

    PubMed  CAS  Google Scholar 

  • Brown CR, Hong-Brown LQ, Welch WJ (1997) Correcting temperature-sensitive protein folding defects. J Clin Invest 99:1432–1444

    PubMed  CAS  Google Scholar 

  • Burrows JA, Willis LK, Perlmutter DH (2000) Chemical chaperones mediate increased secretion of mutant α 1-antitrypsin (α1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in α1-AT deficiency. Proc Natl Acad Sci USA 97:1796–1801

    PubMed  CAS  Google Scholar 

  • Canfield MC, Tamarappoo BK, Moses AM, Verkman AS, Holtzman EJ (1997) Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response. Hum Mol Genet 6:1865–71

    PubMed  CAS  Google Scholar 

  • Cao G, Kuhn A, Dalbey RE (1995) The translocation of negatively charged residues across the membrane is driven by the electrochemical potential: evidence for an electrophoresis-like membrane transfer mechanism. EMBO J 14: 866–875

    PubMed  CAS  Google Scholar 

  • Celesia GG (2001) Disorders of membrane channels or channelopathies. Clin Neurophysiol 112:2–18

    PubMed  CAS  Google Scholar 

  • Chang XB, Cui L, Hou YX, Jensen TJ, Aleksandrov AA, Mengos A, Riordan JR (1999) Removal of multiple arginine-framed trafficking signals overcomes misprocessing of DF508 CFTR present in most patients with cystic fibrosis. Mol Cell 4:137–142

    PubMed  CAS  Google Scholar 

  • Chapple JP, Grayson C, Hardcastle AJ, Saliba RS, van der Spuy J, Cheetham ME (2001) Unfolding retinal dystrophies: a role for molecular chaperones? Trends Mol Med 7:414–421

    PubMed  CAS  Google Scholar 

  • Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW, White GA, O’Riordan CR, Smith AE (1990) Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63: 827–834

    PubMed  CAS  Google Scholar 

  • Chin CN, von Heijne G, de Gier JW (2002) Membrane proteins: shaping up. Trends Biochem Sci 27: 231–234

    PubMed  CAS  Google Scholar 

  • Cohen BE, Lee G, Jacobson KA, Kim YC, Huang Z, Sorscher EJ, Pollard HB (1997) 8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and DF508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator. Biochemistry 36:6455–6461

    PubMed  CAS  Google Scholar 

  • Colby J, Nicholson R, Dickson KM, Orfali W, Naef R, Suter U, Snipes GJ (2000) PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells. Neurobiol Dis 7, 561–573

    PubMed  CAS  Google Scholar 

  • Colley NJ, Cassill JA, Baker EK, Zuker CS (1995) Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. Proc Natl Acad Sci USA 92:3070–3074

    PubMed  CAS  Google Scholar 

  • Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80:795–803

    PubMed  CAS  Google Scholar 

  • Cyr DM, Hohfeld J, Patterson C (2002) Protein quality control: U-box-containing E3 ubiquitin ligases join the fold Trends Biochem. Sci 27:368–375

    CAS  Google Scholar 

  • Danilczyk UG, Cohen-Doyle MF, Williams DB (2000) Functional relationship between calreticulin, calnexin, and the endoplasmic reticulum luminal domain of calnexin. J Biol Chem 275:13089–13097

    PubMed  CAS  Google Scholar 

  • De Vos AM, Ultsch M, Kossiakoff AA (1992) Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255:306–312

    PubMed  Google Scholar 

  • Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, van Oost BA (1994) Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 264:92–95

    PubMed  CAS  Google Scholar 

  • Deen PM, Croes H, van Aubel RA, Ginsel LA, van Os CH (1995) Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing. J Clin Invest 95:2291–2296

    PubMed  CAS  Google Scholar 

  • Delgado-Partin VM, Dalbey RE (1998) The proton motive force, acting on acidic residues, promotes translocation of amino-terminal domains of membrane proteins when the hydrophobicity of the translocation signal is low. J Biol Chem 273:9927–9934

    PubMed  CAS  Google Scholar 

  • Deng WG, Ruan KH, Du M, Saunders MA, Wu KK (2001) Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts. FASEB J 15:2463–2470

    PubMed  CAS  Google Scholar 

  • Denning GM, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ (1992) Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 358:761–764

    PubMed  CAS  Google Scholar 

  • Deschenes SM, Walcott JL, Wexler TL, Scherer SS, Fischbeck KH (1997) Altered trafficking of mutant connexin32. J Neurosci 17:9077–9084

    PubMed  CAS  Google Scholar 

  • Do H, Falcone D, Lin J, Andrews DW, Johnson AE (1996) The cotranslational integration of membrane proteins into the phospholipid bilayer is a multistep process. Cell 85:369–78

    PubMed  CAS  Google Scholar 

  • Dormer RL, Derand R, McNeilly CM, Mettey Y, Bulteau-Pignoux L, Metaye T, Vierfond JM, Gray MA, Galietta LJ, Morris MR, Pereira MM, Doull IJ, Becq F, McPherson MA (2001) Correction of DF508-CFTR activity with benzo(c)quinolizinium compounds through facilitation of its processing in cystic fibrosis airway cells. J Cell Sci 114:4073–4081

    PubMed  CAS  Google Scholar 

  • Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, Sandberg MA, Berson EL (1990a) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366

    PubMed  CAS  Google Scholar 

  • Dryja TP, McGee TL, Hahn LB, Cowley GS, Olsson JE, Reichel E, Sandberg MA, Berson EL (1990b) Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med 323: 1302–1307

    Article  PubMed  CAS  Google Scholar 

  • Durham-Pierre D, Gardner JM, Nakatsu YU, King RA, Francke U, Ching A, Aquaron R, de Marmol V, Brilliant M H (1994) African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Nat Genetics 7:176–179

    CAS  Google Scholar 

  • Edvardsen O, Reiersen AL, Beukers MW, Kristiansen K (2002) tGRAP, the G protein-coupled receptors mutant database. Nucleic Acids Res 30:361–363

    PubMed  CAS  Google Scholar 

  • Ellgaard L, Helenius A (2001) ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 13:431–437

    PubMed  CAS  Google Scholar 

  • Ellgaard L, Riek R, Braun D, Herrmann T, Helenius A, Wührich K (2001a) Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment. FEBS Lett 488:69–73

    PubMed  CAS  Google Scholar 

  • Ellgaard L, Riek R, Herrmann T, Guntert P, Braun D, Helenius A, Wührich K (2001b) NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA 98:3133–3138

    PubMed  CAS  Google Scholar 

  • Farrar GJ, Kenna PF, Humphries P (2002) On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention. EMBO J 21:857–864

    PubMed  CAS  Google Scholar 

  • Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK, et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    PubMed  CAS  Google Scholar 

  • Ficker E, Dennis AT, Obejero-Paz CA, Castaldo P, Taglialatela M, Brown AM (2000a) Retention in the endoplasmic reticulum as a mechanism of dominant-negative current suppression in human long QT syndrome. J Mol Cell Cardiol 32:2327–2337

    PubMed  CAS  Google Scholar 

  • Ficker E, Thomas D, Viswanathan PC, Dennis AT, Priori SG, Napolitano C, Memmi M, Wible BA, Kaufman ES, Iyengar S, Schwartz PJ, Rudy Y, Brown AM (2000b) Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome. Am J Physiol Heart Circ Physiol 279:H1748–1756

    PubMed  CAS  Google Scholar 

  • Ficker E, Obejero-Paz CA, Zhao S, Brown AM (2002) The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations. J Biol Chem 277:4989–4998

    PubMed  CAS  Google Scholar 

  • Ficker E, Dennis AT, Wang L, Brown AM (2003) Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Circ Res 92:e87–100

    PubMed  Google Scholar 

  • Fiedler K, Parton RG, Kellner R, Etzold T, Simons K (1994) VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in epithelial cells. EMBO J 13:1729–1740

    PubMed  CAS  Google Scholar 

  • Fiedler K, Veit M, Stamnes MA, Rothman JE (1996) Bimodal interaction of coatomer with the p24 family of putative cargo receptors. Science 273:1396–1399

    PubMed  CAS  Google Scholar 

  • Fleming RE, Sly WS (2002) Mechanisms of iron accumulation in hereditary hemochromatosis Annu Rev Physiol. 64:663–680

    PubMed  CAS  Google Scholar 

  • Francis E, Wang N, Parag H, Halaban R, Hebert DN (2003) Tyrosinase maturation and oligomerization in the endoplasmic reticulum require a melanocyte-specific factor. J Biol Chem 278:25607–25617

    PubMed  CAS  Google Scholar 

  • Frank SJ (2002) Receptor dimerization in GH and erythropoietin action—it takes two to tango, but how? Endocrinology 143:2–10

    PubMed  CAS  Google Scholar 

  • Fransen JA, Hauri HP, Ginsel LA, Naim HY (1991) Naturally occurring mutations in intestinal sucrase-isomaltase provide evidence for the existence of an intracellular sorting signal in the isomaltase subunit. J Cell Biol 115: 45–57

    PubMed  CAS  Google Scholar 

  • Frederick JM, Krasnoperova NV, Hoffmann K, Church-Kopish J, Ruther K, Howes K, Lem J, Baehr W (2001) Mutant rhodopsin transgene expression on a null background. Invest Ophthalmol Vis Sci 42:826–833

    PubMed  CAS  Google Scholar 

  • Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S (1993) Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 361:549–552

    PubMed  CAS  Google Scholar 

  • Furutani M, Trudeau MC, Hagiwara N, Seki A, Gong Q, Zhou Z, Imamura S, Nagashima H, Kasanuki H, Takao A, Momma K, January CT, Robertson GA, Matsuoka R (1999) Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel. Circulation 99: 2290–2294

    PubMed  CAS  Google Scholar 

  • Furman I, Cook O, Kasir J, Low W, Rahamimoff H (1995) The putative amino-terminal signal peptide of the cloned rat brain Na(+)-Ca2+ exchanger gene (RBE-1) is not mandatory for functional expression. J Biol Chem 270: 19120–19127

    PubMed  CAS  Google Scholar 

  • Gething MJ (1999) Role and regulation of the ER chaperone BiP Semin Cell Dev Biol 10:465–72

    CAS  Google Scholar 

  • Gilbert A, Jadot M, Leontieva E, Wattiaux-De Coninck S, Wattiaux R (1998) DF508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells. Exp Cell Res 242:144–52

    PubMed  CAS  Google Scholar 

  • Gilmore R, Blobel G (1983) Transient involvement of signal recognition particle and its receptor in the microsomal membrane prior to protein translocation. Cell 35:677–685

    PubMed  CAS  Google Scholar 

  • Giraudo CG, Maccioni HJ (2003) Endoplasmic reticulum export of glycosyltransferases depends on interaction of a cytoplasmic dibasic motif with Sar1. Mol Biol Cell 14:3753–3766

    PubMed  CAS  Google Scholar 

  • Goder V, Spiess M (2001) Topogenesis of membrane proteins: determinants and dynamics. FEBS Lett 504: 87–93

    PubMed  CAS  Google Scholar 

  • Godowski PJ, Leung DW, Meacham LR, Galgani JP, Hellmiss R, Keret R, Rotwein PS, Parks JS, Laron Z, Wood WI (1989) Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci USA 86:8083–8087

    PubMed  CAS  Google Scholar 

  • Goldstein JL, Brown MS, Stone NJ (1977) Genetics of the LDL receptor: evidence that the mutations affecting binding and internalization are allelic. Cell 12:629–641

    PubMed  CAS  Google Scholar 

  • Goldstein JL, Brown MS (1979) The LDL receptor locus and the genetics of familial hypercholesterolemia. Annu Rev Genet 13:259–89

    PubMed  CAS  Google Scholar 

  • Görlich D, Prehn S, Hartmann E, Kalies KU, Rapoport TA (1992) A mammalian homolog of SEC61p and SECYp is associated with ribosomes and nascent polypeptides during translocation. Cell 71:489–503

    PubMed  Google Scholar 

  • Görlich D, Rapoport TA (1993) Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membrane. Cell 75:615–30

    PubMed  Google Scholar 

  • Gorvel JP, Ferrero A, Chambraud L, Rigal A, Bonicel J, Maroux S (1991) Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon. Gastroenterology 101:618–625

    PubMed  CAS  Google Scholar 

  • Gow A, Friedrich VL Jr, Lazzarini RA (1994) Many naturally occurring mutations of myelin proteolipid protein impair its intracellular transport. J Neurosci Res 37:574–583

    PubMed  CAS  Google Scholar 

  • Gow A, Southwood CM, Lazzarini RA (1998) Disrupted proteolipid protein trafficking results in oligodendrocyte apoptosis in an animal model of Pelizaeus-Merzbacher disease. J Cell Biol 140:925–934

    PubMed  CAS  Google Scholar 

  • Haardt M, Benharouga M, Lechardeur D, Kartner N, Lukacs GL (1999) C-terminal truncations destabilize the cystic fibrosis transmembrane conductance regulator without impairing its biogenesis A novel class of mutation. J Biol Chem 274:21873–21877

    PubMed  CAS  Google Scholar 

  • Halaban R, Svedine S, Cheng E, Smicum Y, Aron R, Hebert DN (2000) Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proc Natl Acad Sci USA 97:5889–5894

    PubMed  CAS  Google Scholar 

  • Hammond C, Helenius A (1994a) Folding of VSV G protein: sequential interaction with BiP and calnexin. Science 266:456–458

    PubMed  CAS  Google Scholar 

  • Hammond C, Helenius A (1994b) Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. J Cell Biol 126: 41–52

    PubMed  CAS  Google Scholar 

  • Harley CA, Tipper DJ (1996) The role of charged residues in determining transmembrane protein insertion orientation in yeast. J Biol Chem 271:24625–24633

    PubMed  CAS  Google Scholar 

  • Harley CA, Holt JA, Turner R, Tipper DJ (1998) Transmembrane protein insertion orientation in yeast depends on the charge difference across transmembrane segments, their total hydrophobicity, and its distribution. J Biol Chem 273:24963–24971

    PubMed  CAS  Google Scholar 

  • Hartmann E, Rapoport TA, Lodish HF (1989) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci, USA 86:5786–5790

    PubMed  CAS  Google Scholar 

  • Hauri HP, Quaroni A, Isselbacher KJ (1979) Biogenesis of intestinal plasma membrane: posttranslational route and cleavage of sucrase-isomaltase. Proc Natl Acad Sci USA 76:5183–5186

    PubMed  CAS  Google Scholar 

  • Hauri H, Appenzeller C, Kuhn F, Nufer (2000) Lectins and traffic in the secretory pathway. FEBS Lett 476:32–37

    PubMed  CAS  Google Scholar 

  • Heda GD, Tanwani M, Marino CR (2001) The Delta F508 mutation shortens the biochemical half-life of plasma membrane CFTR in polarized epithelial cells Am J Physiol Cell Physiol. 280:C166–174

    PubMed  CAS  Google Scholar 

  • Heinrich SU, Mothes W, Brunner J, Rapoport TA (2000) The Sec61p complex mediates the integration of a membrane protein by allowing lipid partitioning of the transmembrane domain. Cell 102:233–244

    PubMed  CAS  Google Scholar 

  • Heinrich SU, Rapoport TA (2003) Cooperation of transmembrane segments during the integration of a double-spanning protein into the ER membrane. EMBO J 22:3654–3663

    PubMed  CAS  Google Scholar 

  • Hermann JM, Malkus P, Schekman R (1999) Out of the ER-outfitters, escorts and guides. Trends Cell Biol 9: 5–7

    Google Scholar 

  • Hermosilla R, Schülein R (2001) Sorting functions of the individual cytoplasmic domains of the G protein-coupled vasopressin V2 receptor in Madin Darby canine kidney epithelial cells. Mol Pharmacol 60: 1031–1039

    PubMed  CAS  Google Scholar 

  • Heymann JA, Subramaniam S (1997) Expression, stability, and membrane integration of truncation mutants of bovine rhodopsin. Proc Natl Acad Sci USA 94:4966–48971

    PubMed  CAS  Google Scholar 

  • Hobbs HH, Russell DW, Brown MS, Goldstein JL (1990) The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu Rev Genet 24:133–170

    PubMed  CAS  Google Scholar 

  • Horn F, Weare J, Beukers MW, Horsch S, Bairoch A, Chen W, Edvardsen O, Campagne F, Vriend G (1998) GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Res 26:275–279

    PubMed  CAS  Google Scholar 

  • Hübner CA, Jentsch TJ (2002) Ion channel diseases Hum Mol Genet 11:2435–2445

    PubMed  Google Scholar 

  • Hunziker W, Fumey C (1994) A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells. EMBO J 13:2963–2967

    PubMed  CAS  Google Scholar 

  • Hull KL, Harvey S (1999) Growth hormone resistance: clinical states and animal models. J Endocrinol 163: 165–172

    PubMed  CAS  Google Scholar 

  • Inglehearn CF, Tarttelin EE, Plant C, Peacock RE, al-Maghtheh M, Vithana E, Bird AC, Bhattacharya SS (1998) A linkage survey of 20 dominant retinitis pigmentosa families: frequencies of the nine known loci and evidence for further heterogeneity. J Med Genet 35:1–5

    PubMed  CAS  Google Scholar 

  • Innamorati G, Sadeghi H, Birnbaumer M (1996) A fully active nonglycosylated V2 vasopressin receptor. Mol Pharmacol 50:467–473

    PubMed  CAS  Google Scholar 

  • Jacob R, Zimmer KP, Schmitz J, Naim HY (2000) Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme. J Clin Invest 106:281–287

    PubMed  CAS  Google Scholar 

  • Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR (1995) Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83:129–135

    PubMed  CAS  Google Scholar 

  • Jørgensen MM, Jensen ON, Holst HU, Hansen JJ, Corydon TJ, Bross P, Bolund L, Gregersen N (2000) Grp78 is involved in retention of mutant low density lipoprotein receptor protein in the endoplasmic reticulum. J Biol Chem 275:33861–33868

    PubMed  Google Scholar 

  • Kamsteeg EJ, Wormhoudt TA, Rijss JP, van Os CH, Deen PM (1999) An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus. EMBO J 18: 2394–2400

    PubMed  CAS  Google Scholar 

  • Kappeler F, Klopfenstein DR, Foguet M, Paccaud JP, Hauri HP (1997) The recycling of ERGIC-53 in the early secretory pathway ERGIC-53 carries a cytosolic endoplasmic reticulum-exit determinant interacting with COPII. J Biol Chem 272:31801–31808

    PubMed  CAS  Google Scholar 

  • Kiefer D, Hu X, Dalbey R, Kuhn A (1997) Negatively charged amino acid residues play an active role in orienting the Sec-independent Pf3 coat protein in the Escherichia coli inner membrane. EMBO J 16:2197–2204

    PubMed  CAS  Google Scholar 

  • Klumperman J, Schweizer A, Clausen H, Tang BL, Hong W, Oorschot V, Hauri HP (1998) The recycling pathway of protein ERGIC-53 and dynamics of the ER-Golgi intermediate compartment. J Cell Sci 11:3411–3425

    Google Scholar 

  • Klumperman J (2000) Transport between ER and Golgi Curr Opin Cell Biol 12:445–449

    PubMed  CAS  Google Scholar 

  • Knoers NV, Deen PM (2001) Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol 16:1146–1152

    PubMed  CAS  Google Scholar 

  • Ko YH, Pedersen PL (2001) Cystic fibrosis: a brief look at some highlights of a decade of research focused on elucidating and correcting the molecular basis of the disease. J Bioenerg Biomembr 33:513–521

    PubMed  CAS  Google Scholar 

  • Köchl R, Alken M, Rutz C, Krause G, Oksche A, Rosenthal W, Schülein R (2002) The signal peptide of the G protein-coupled human endothelin B receptor is necessary for translocation of the N-terminal tail across the endoplasmic reticulum membrane. J Biol Chem 277:16131–16138

    PubMed  Google Scholar 

  • Krause G, Hermosilla R, Oksche A, Rutz C, Rosenthal W, Schülein R (2000) Molecular and conformational features of a transport-relevant domain in the C-terminal tail of the vasopressin V2 receptor. Mol Pharmacol 57: 232–242

    PubMed  CAS  Google Scholar 

  • Kuehn MJ, Herrmann JM, Schekman R (1998) COPII-cargo interactions direct protein sorting into ER-derived transport vesicles. Nature 391:187–190

    PubMed  CAS  Google Scholar 

  • Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S (2001) Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet 69:738–748

    PubMed  CAS  Google Scholar 

  • Laron Z, Klinger B, Eshet R, Kaneti H, Karasik A, Silbergeld A (1993) Laron syndrome due to a post-receptor defect: response to IGF-I treatment. Isr J Med Sci 29:757–763

    PubMed  CAS  Google Scholar 

  • Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FS 2nd, Mori Y, Campbell KP, Frankel WN (1998) The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat Genet 19:340–347

    PubMed  CAS  Google Scholar 

  • Li T, Snyder WK, Olsson JE, Dryja TP (1996) Transgenic mice carrying the dominant rhodopsin mutation P347S: evidence for defective vectorial transport of rhodopsin to the outer segments. Proc Natl Acad Sci USA 93: 14176–14181

    PubMed  CAS  Google Scholar 

  • Loo TW, Ho C, Clarke DM (1995) Expression of a functionally active human renal sodium-calcium exchanger lacking a signal sequence. J Biol Chem 270:19345–19350

    PubMed  CAS  Google Scholar 

  • Lorenz D, Krylov A, Hahm D, Hagen V, Rosenthal W, Pohl P, Maric K (2003) Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin-2 in renal epithelial cells. EMBO Rep 4:88–93

    PubMed  CAS  Google Scholar 

  • Loffing J, Moyer BD, Reynolds D, Stanton BA (1999) PBA increases CFTR expression but at high doses inhibits Cl-secretion in Calu-3 airway epithelial cells. Am J Physiol 277:L700–708

    PubMed  CAS  Google Scholar 

  • Lu Y, Xiong X, Helm A, Kimani K, Bragin A, Skach WR (1998) Co-and posttranslational translocation mechanisms direct cystic fibrosis transmembrane conductance regulator N terminus transmembrane assembly. J Biol Chem 273: 568–576

    PubMed  CAS  Google Scholar 

  • Ma D, Zerangue N, Lin YF, Collins A, Yu M, Jan YN, Jan LY (2001) Role of ER export signals in controlling surface potassium channel numbers. Science 291:316–319

    PubMed  CAS  Google Scholar 

  • Malkus P, Jiang F, Schekman R (2002) Concentrative sorting of secretory cargo proteins into COPII-coated vesicles. J Cell Biol 159:915–921

    PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Jan YN, Jan LY (2000) A trafficking checkpoint controls GABAB receptor heterodimerization. Neuron 27:97–106

    Google Scholar 

  • Marr N, Bichet DG, Hoefs S, Savelkoul PJ, Konings IB, De Mattia F, Graat MP, Arthus MF, Lonergan M, Fujiwara TM, Knoers NV, Landau D, Balfe WJ, Oksche A, Rosenthal W, Müller D, Van Os CH, Deen PM (2002a) Cell-biologic and functional analyses of five new aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol 13:2267–77

    PubMed  CAS  Google Scholar 

  • Marr N, Bichet DG, Lonergan M, Arthus MF, Jeck N, Seyberth HW, Rosenthal W, van Os CH, Oksche A, Deen PM (2002b) Heteroligomerization of an aquaporin-2 mutant with wild-type aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus. Hum Mol Genet 11:779–789

    PubMed  CAS  Google Scholar 

  • Martin PE, Coleman SL, Casalotti SO, Forge A, Evans WH (1999) Properties of connexin26 gap junctional proteins derived from mutations associated with non-syndromal hereditary deafness. Hum Mol Genet 8:2369–76

    PubMed  CAS  Google Scholar 

  • Martin PE, Mambetisaeva ET, Archer DA, George CH, Evans WH (2000) Analysis of gap junction assembly using mutated connexins detected in Charcot-Marie-Tooth X-linked disease. J Neurochem 74:711–720

    PubMed  CAS  Google Scholar 

  • Martinez-Ménarguez JA, Geuze HJ, Slot JW, Klumperman J (1999) Vesicular tubular clusters between the ER and Golgi mediate concentration of soluble secretory proteins by exclusion from COPI-coated vesicles. Cell 98: 81–90

    PubMed  Google Scholar 

  • Martoglio B, Hofmann MW, Brunner J, Dobberstein B (1995) The protein-conducting channel in the membrane of the endoplasmic reticulum is open laterally toward the lipid bilayer. Cell 81:207–214

    PubMed  CAS  Google Scholar 

  • Matter K, Hunziker W, Mellman I (1992) Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants. Cell 71:741–753

    PubMed  CAS  Google Scholar 

  • Meacham GC, Lu Z, King S, Sorscher E, Tousson A, Cyr DM (1999) The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. EMBO J 18:1492–1505

    PubMed  CAS  Google Scholar 

  • Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol 3:100–105

    PubMed  CAS  Google Scholar 

  • Mehta A, Lu X, Block TM, Blumberg BS, Dwek RA (1997) Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion. Proc Natl Acad Sci USA 94:1822–1827

    PubMed  CAS  Google Scholar 

  • Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ (1997) Global prevalence of putative haemochromatosis mutations. J Med Genet 34:275–278

    Article  PubMed  CAS  Google Scholar 

  • Miller EA, Beilharz TH, Malkus PN, Lee MC, Hamamoto S, Orci L, Schekman R (2003) Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. Cell 114: 497–509

    PubMed  CAS  Google Scholar 

  • Molinari M, Helenius A (2000) Chaperone selection during glycoprotein translocation into the endoplasmic reticulum. Science 288:331–333

    PubMed  CAS  Google Scholar 

  • Moolenaar CE, Ouwendijk J, Wittpoth M, Wisselaar HA, Hauri HP, Ginsel LA, Naim HY, Fransen JA (1997) A mutation in a highly conserved region in brush-border sucrase-isomaltase and lysosomal alpha-glucosidase results in Golgi retention. J Cell Sci 110:557–567

    PubMed  CAS  Google Scholar 

  • Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petaja-Repo U, Angers S, Morin D, Bichet DG, Bouvier M (2000a) Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105:887–895

    PubMed  CAS  Google Scholar 

  • Morello JP, Petaja-Repo UE, Bichet DG, Bouvier M (2000b) Pharmacological chaperones: a new twist on receptor folding. Trends Pharmacol Sci 21:466–469

    PubMed  CAS  Google Scholar 

  • Morello JP, Salahpour A, Petaja-Repo UE, Laperriere A, Lonergan M, Arthus MF, Nabi IR, Bichet DG, Bouvier M (2001) Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry 40:6766–6775

    PubMed  CAS  Google Scholar 

  • Morello JP, Bichet DG (2001) Nephrogenic diabetes insipidus. Annu Rev Physiol 63:607–30

    PubMed  CAS  Google Scholar 

  • Moritz OL, Tam BM, Papermaster DS, an Nakayama T (2001) A functional rhodopsin-green fluorescent protein fusion protein localizes correctly in transgenic Xenopus laevis retinal rods and is expressed in a time-dependent pattern. J Biol Chem 276:28242–28251

    PubMed  CAS  Google Scholar 

  • Mothes W, Heinrich SU, Graf R, Nilsson I, von Heijne G, Brunner J, Rapoport TA (1997) Molecular mechanism of membrane protein integration into the endoplasmic reticulum. Cell 89:523–33

    PubMed  CAS  Google Scholar 

  • Moussalli M, Pipe SW, Hauri HP, Nichols WC, Ginsburg D, Kaufman RJ (1999) Mannose-dependent endoplasmic reticulum (ER)-Golgi intermediate compartment-53-mediated ER to Golgi trafficking of coagulation factors V and VIII. J Biol Chem 274:32539–32542

    PubMed  CAS  Google Scholar 

  • Moyer BD, Loffing-Cueni D, Loffing J, Reynolds D, Stanton BA (1999) Butyrate increases apical membrane CFTR but reduces chloride secretion in MDCK cells. Am J Physiol 277:F271–276

    PubMed  CAS  Google Scholar 

  • Mulders SM, Knoers NV, Van Lieburg AF, Monnens LA, Leumann E, Wuhl E, Schober E, Rijss JP, Van Os CH, Deen PM (1997) New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels. J Am Soc Nephrol 8:242–248

    PubMed  CAS  Google Scholar 

  • Mulders SM, Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM (1998) An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest 102:57–66

    PubMed  CAS  Google Scholar 

  • Muniz M, Nuoffer C, Hauri HP, Riezman H (2000) The Emp24 complex recruits a specific cargo molecule into endoplasmic reticulum-derived vesicles. J Cell Biol 148:925–930

    PubMed  CAS  Google Scholar 

  • Naef R, Adlkofer K, Lescher B, Suter U (1997) Aberrant protein trafficking in Trembler suggests a disease mechanism for hereditary human peripheral neuropathies. Mol Cell Neurosci 9:13–25

    PubMed  CAS  Google Scholar 

  • Naef R, Suter U (1999) Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Neurobiol Dis 6:1–14

    PubMed  CAS  Google Scholar 

  • Naim HY, Roth J, Sterchi EE, Lentze M, Milla P, Schmitz J, Hauri HP (1988a) Sucrase-isomaltase deficiency in humans Different mutations disrupt intracellular transport, processing, and function of an intestinal brush border enzyme. J Clin Invest 82:667–679

    PubMed  CAS  Google Scholar 

  • Naim HY, Sterchi EE, Lentze MJ (1988b) Structure, biosynthesis, and glycosylation of human small intestinal maltase-glucoamylase. J Biol Chem 263:19709–19717

    PubMed  CAS  Google Scholar 

  • Neerman-Arbez M, Johnson KM, Morris MA, McVey JH, Peyvandi F, Nichols WC, Ginsburg D, Rossier C, Antonarakis SE, Tuddenham EG (1999) Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency. Blood 93:2253–2260

    PubMed  CAS  Google Scholar 

  • Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant M H (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism. Am J Hum Gen 69:981–988

    CAS  Google Scholar 

  • Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, Moussalli MJ, Hauri HP, Ciavarella N, Kaufman RJ, Ginsburg D (1998) Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII. Cell 93:61–70

    PubMed  CAS  Google Scholar 

  • Nichols WC, Terry VH, Wheatley MA, Yang A, Zivelin A, Ciavarella N, Stefanile C, Matsushita T, Saito H, de Bosch NB, Ruiz-Saez A, Torres A, Thompson AR, Feinstein DI, White GC, Negrier C, Vinciguerra C, Aktan M, Kaufman RJ, Ginsburg D, Seligsohn U (1999) Protein ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood 93:2261–2266

    PubMed  CAS  Google Scholar 

  • Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA (2002) Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205–244

    PubMed  CAS  Google Scholar 

  • Nilsson I, Witt S, Kiefer H, Mingarro I, von Heijne G (2000) Distant downstream sequence determinants can control N-tail translocation during protein insertion into the endoplasmic reticulum membrane. J Biol Chem 275: 6207–6213

    PubMed  CAS  Google Scholar 

  • Nimpf J, Schneider WJ (2000) From cholesterol transport to signal transduction: low density lipoprotein receptor, very low density lipoprotein receptor, and apolipoprotein E receptor-2. Biochim Biophys Acta 1529:287–298

    PubMed  CAS  Google Scholar 

  • Nishimura N, Balch WE (1997) A di-acidic signal required for selective export from the endoplasmic reticulum. Science 277:556–558

    PubMed  CAS  Google Scholar 

  • Nishimura N, Bannykh S, Slabough S, Matteson J, Altschuler Y, Hahn K, Balch WE (1999) A di-acidic (DXE) code directs concentration of cargo during export from the endoplasmic reticulum. J Biol Chem 274:15937–15946

    PubMed  CAS  Google Scholar 

  • Noiva R (1999) Protein disulfide isomerase: the multifunctional redox chaperone of the endoplasmic reticulum. Semin Cell Dev Biol 10:481–493

    PubMed  CAS  Google Scholar 

  • Noorwez SM, Kuksa V, Imanishi Y, Zhu L, Filipek S, Palczewski K, Kaushal S (2003) Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem 278:14442–14450

    PubMed  CAS  Google Scholar 

  • Nufer O, Kappeler F, Guldbrandsen S, Hauri HP (2003) ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci 116:4429–4440

    PubMed  CAS  Google Scholar 

  • Oetting WS, King RA (1999) Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat 13:99–115

    PubMed  CAS  Google Scholar 

  • Okada T, Palczewski K (2001) Crystal structure of rhodopsin: implications for vision and beyond. Curr Opin Struct Biol 11:420–426

    PubMed  CAS  Google Scholar 

  • Oksche A, Schülein R, Rutz C, Liebenhoff U, Dickson J, Müller H, Birnbaumer M, Rosenthal W (1996) Vasopressin V2 receptor mutants causing X-linked nephrogenic diabetes insipidus: analysis of expression, processing and function. Mol Pharmacol 50:820–828

    PubMed  CAS  Google Scholar 

  • Oksche A, Dehe M, Schülein R, Wiesner B, Rosenthal W (1998) Folding and cell surface expression of the vasopressin V2 receptor: requirement of the intracellular C-terminus. FEBS Lett 424:57–62

    PubMed  CAS  Google Scholar 

  • Oksche A, Rosenthal W (1998) The molecular basis of nephrogenic diabetes insipidus. J Mol Med 76:326–327

    PubMed  CAS  Google Scholar 

  • Oksche A, Leder G, Valet S, Platzer M, Hasse K, Geist G, Krause G, Rosenthal A, Rosenthal W (2002) Variant amino acids in the extracellular loops of murine and human vasopressin V2 receptors account for differences in cell surface expression and ligand affinity. Mol Endocrinol 16:799–813

    PubMed  CAS  Google Scholar 

  • Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW (1999) A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 341:718–724

    PubMed  CAS  Google Scholar 

  • Ott CM, Lingappa VR (2002) Integral membrane protein biosynthesis: why topology is hard to predict. J Cell Sci 115:2003–2009

    PubMed  CAS  Google Scholar 

  • Ouwendijk J, Moolenaar CE, Peters WJ, Hollenberg CP, Ginsel LA, Fransen JA, Naim HY (1996) Congenital sucrase-isomaltase deficiency Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment. J Clin Invest 97:633–641

    PubMed  CAS  Google Scholar 

  • Ouzzine M, Magdalou J, Burchell B, Fournel-Gigleux S (1999a) Expression of a functionally active human hepatic UDP-glucuronosyltransferase (UGT1A6) lacking the N-terminal signal sequence in the endoplasmic reticulum. FEBS Lett 454:87–91

    Google Scholar 

  • Ouzzine M, Magdalou J, Burchell B, Fournel-Gigleux S (1999b) An internal signal sequence mediates the targeting and retention of the human UDP-glucuronosyltransferase 1A6 to the endoplasmic reticulum. J Biol Chem 274: 31401–31409

    PubMed  CAS  Google Scholar 

  • Owens D J, Evans PR (1998) A structural explanation for the recognition of tyrosine based endocytotic signals. Science 282:1327–1332

    Google Scholar 

  • Pagano A, Rovelli G, Mosbacher J, Lohmann T, Duthey B, Stauffer D, Ristig D, Schuler V, Meigel I, Lampert C, Stein T, Prezeau L, Blahos J. Pin J, Froestl W, Kuhn R, Heid J, Kaupmann K, Bettler B (2001) C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABAb receptors. J Neurosci 21:1189–1202

    PubMed  CAS  Google Scholar 

  • Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–745

    PubMed  CAS  Google Scholar 

  • Pan Y, Wilson P, Gitschier J (1994) The effect of eight V2 vasopressin receptor mutations on stimulation of adenylyl cyclase and binding to vasopressin. J Biol Chem 269:31933–31937

    PubMed  CAS  Google Scholar 

  • Parodi AJ (2000) Protein glucosylation and its role in protein folding. Annu Rev Biochem 69:69–93

    PubMed  CAS  Google Scholar 

  • Pasyk EA, Foskett JK (1995) Mutant (DF508) cystic fibrosis transmembrane conductance regulator Cl-channel is functional when retained in endoplasmic reticulum of mammalian cells. J Biol Chem 270:12347–12350

    PubMed  CAS  Google Scholar 

  • Paulussen A, Raes A, Matthijs G, Snyders DJ, Cohen N, Aerssens J (2002) A novel mutation (T65P) in the PAS domain of the human potassium channel HERG results in the long QT syndrome by trafficking deficiency. J Biol Chem 277: 48610–48616

    PubMed  CAS  Google Scholar 

  • Peng R, Grabowski R, De Antoni A, Gallwitz D (1999) Specific interaction of the yeast cis-Golgi syntaxin Sed5p and the coat protein complex II component Sec24p of endoplasmic reticulum-derived transport vesicles. Proc Natl Acad Sci USA 96:3751–3756

    PubMed  CAS  Google Scholar 

  • Petaja-Repo UE, Hogue M, Bhalla S, Laperriere A, Morello JP, Bouvier M (2002) Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBO J 21:1628–37

    PubMed  CAS  Google Scholar 

  • Phelan JK, Bok D (2000) A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes Mol Vis 6:116–124

    PubMed  CAS  Google Scholar 

  • Pind S, Riordan JR, Williams DB (1994) Participation of the endoplasmic reticulum chaperone calnexin (p88,IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 269:12784–12788

    PubMed  CAS  Google Scholar 

  • Postina R, Ufer E, Pfeiffer R, Knoers NV, Fahrenholz F (2000) Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congenital nephrogenic diabetes insipidus. Mol Cell Endocrinol 164: 31–39

    PubMed  CAS  Google Scholar 

  • Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm ML, Ianuzzi MC, Collins FS, Tsui LC (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073

    PubMed  CAS  Google Scholar 

  • Risler JL, Delorme MO, Delacroix H, Henaut A (1988) Amino acid substitutions in structurally related proteins A pattern recognition approach Determination of a new and efficient scoring matrix. J Mol Biol 204:1019–1029

    PubMed  CAS  Google Scholar 

  • Rodriguez MC, Xie YB, Wang H, Collison K, Segaloff L (1992) Effects of truncations of the cytoplasmic tail of the luteinizing hormone/chorionic gonadotropin receptor on receptor-mediated hormone internalization. Mol Endocrinol 6:327–336

    PubMed  CAS  Google Scholar 

  • Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG (1992) Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 359:233–235

    PubMed  CAS  Google Scholar 

  • Rothman JE (1994) Mechanisms of intracellular protein transport. Nature 372:55–63

    PubMed  CAS  Google Scholar 

  • Roti EC, Myers CD, Ayers RA, Boatman DE, Delfosse SA, Chan EK, Ackerman MJ, January CT, Robertson GA (2002) Interaction with GM130 during HERG ion channel trafficking Disruption by type 2 congenital long QT syndrome mutations Human Ether-a-go-go-Related Gene. J Biol Chem 277:47779–47785

    PubMed  CAS  Google Scholar 

  • Rubenstein RC, Egan ME, Zeitlin PL (1997) In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing DF508-CFTR. J Clin Invest 100: 2457–2465

    Article  PubMed  CAS  Google Scholar 

  • Rutz C, Rosenthal W, Schülein R (1999) A single negatively charged residue affects the orientation of a membrane protein in the inner membrane of Escherichia coli only when it is located adjacent to a transmembrane domain. J Biol Chem 274:33757–33763

    PubMed  CAS  Google Scholar 

  • Ryan MC, Notterpek L, Tobler AR, Liu N, Shooter EM (2000) Role of the peripheral myelin protein 22 N-linked glycan in oligomer stability. J Neurochem 75:1465–1474

    PubMed  CAS  Google Scholar 

  • Sadeghi HM, Innamorati G, Birnbaumer M (1997) An X-linked NDI mutation reveals a requirement for cell surface V2R expression. Mol Endocrinol 11:706–713

    PubMed  CAS  Google Scholar 

  • Sadtler S, Laube B, Lashub A, Nicke A, Betz H, Schmalzing G (2003) A basic cluster determines topology of the cytoplasmic M3-M4 loop of the glycine receptor alpha1 subunit. J Biol Chem 278:16782–16790

    PubMed  CAS  Google Scholar 

  • Sanders CR, Ismail-Beigi F, McEnery MW (2001) Mutations of peripheral myelin protein 22 result in defective trafficking through mechanisms which may be common to diseases involving tetraspan membrane proteins. Biochemistry 40:9453–9459

    PubMed  CAS  Google Scholar 

  • Sato S, Ward CL, Krouse ME, Wine JJ, Kopito RR (1996) Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J Biol Chem 271:635–638

    PubMed  CAS  Google Scholar 

  • Sato M, Hresko R, Mueckler M (1998) Testing the charge difference hypothesis for the assembly of a eucaryotic multispanning membrane protein. J Biol Chem 273:25203–25208

    PubMed  CAS  Google Scholar 

  • Savage MO, Burren CP, Blair JC, Woods KA, Metherell L, Clark AJ, Camacho-Hubner C (2001) Growth hormone insensitivity: pathophysiology, diagnosis, clinical variation and future perspectives. Horm Res 55 Suppl 2: 32–35

    PubMed  CAS  Google Scholar 

  • Schekman R, Orci L (1996) Coat proteins and vesicle budding. Science 271:1526–1533

    PubMed  CAS  Google Scholar 

  • Schöneberg T, Liu J, Wess J (1995) Plasma membrane localization and functional rescue of truncated forms of a G protein-coupled receptor. J Biol Chem 270:18000–18006

    PubMed  Google Scholar 

  • Schöneberg T, Yun J, Wenkert D, Wess J (1996) Functional rescue of mutant V2 vasopressin receptors causing nephrogenic diabetes insipidus by a co-expressed receptor polypeptide. EMBO J 15:1283–91

    PubMed  Google Scholar 

  • Schrag JD, Bergeron JJ, Li Y, Borisova S, Hahn M, Thomas DY, Cygler M (2001) The Structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell 8:633–644

    PubMed  CAS  Google Scholar 

  • Schülein R, Rutz C, Rosenthal W (1996a) Membrane targeting and determination of transmembrane topology of the human vasopressin V2 receptor. J Biol Chem 271:28844–28852

    PubMed  Google Scholar 

  • Schülein R, Liebenhoff U, Müller H, Birnbaumer M, Rosenthal W (1996b) Properties of the human arginine vasopressin V2 receptor after site-directed mutagenesis of its putative palmitoylation site. Biochem J 313:611–616

    PubMed  Google Scholar 

  • Schülein R, Hermosilla R, Oksche A, Dehe M, Wiesner B, Krause G, Rosenthal W (1998a) A di-leucine sequence and an upstream glutamate residue in the intracellular C-terminus of the vasopressin V2 receptor are essential for cell surface transport. Mol Pharmacol 54:525–535

    PubMed  Google Scholar 

  • Schülein R, Lorenz D, Oksche A, Wiesner B, Hermosilla R, Ebert J, Rosenthal W (1998b) Polarized cell surface expression of the G protein-coupled vasopressin V2 receptor in Madin Darby canine kidney cells. FEBS Lett 441:170–176

    PubMed  Google Scholar 

  • Schülein R, Zühlke K, Oksche A, Furkert J, Rosenthal W (2000) The role of conserved extracellular cysteine residues in vasopressin V2 receptor function and properties of two naturally occurring mutant receptors with additional extracellular cysteine residues. FEBS Lett 466:101–106

    PubMed  Google Scholar 

  • Schülein R, Zühlke K, Krause G, Rosenthal W (2001) Functional rescue of the nephrogenic diabetes insipidus causing vasopressin V2 receptor mutants G185C and R202C by a second site suppressor mutation. J Biol Chem 276:8384–8392

    PubMed  Google Scholar 

  • Schwiebert EM, Benos DJ, Egan ME, Stutts MJ, Guggino WB (1999) CFTR is a conductance regulator as well as a chloride channel. Physiol Rev 79:S145–S66

    PubMed  CAS  Google Scholar 

  • Scott DB, Blanpied TA, Swanson GT, Zhang C, Ehlers MD (2001) An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J Neurosci 21:3063–72

    PubMed  CAS  Google Scholar 

  • Sevier CS, Weisz OA, Davis M, Machamer CE (2000) Efficient export of the vesicular stomatitis virus G protein from the endoplasmic reticulum requires a signal in the cytoplasmic tail that includes both tyrosine-based and di-acidic motifs. Mol Biol Cell 11:13–22

    PubMed  CAS  Google Scholar 

  • Sharma M, Benharouga M, Hu W, Lukacs GL (2001) Conformational and temperature-sensitive stability defects of the ΔF508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J Biol Chem 276:8942–8950

    PubMed  CAS  Google Scholar 

  • Sheppard DN, Welsh MJ (1999) Structure and function of the CFTR chloride channel. Physiol Rev 79:S23–S45

    PubMed  CAS  Google Scholar 

  • Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (1999) Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285:103–106

    PubMed  CAS  Google Scholar 

  • Smilde TJ, van Wissen S, Wollersheim H, Kastelein JJ, Stalenhoef AF (2001) Genetic and metabolic factors predicting risk of cardiovascular disease in familial hypercholesterolemia. Neth J Med 59:184–195

    PubMed  CAS  Google Scholar 

  • Sousa MC, Ferrero-Garcia MA, Parodi AJ (1992) Recognition of the oligosaccharide and protein moieties of glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. Biochemistry 31:97–105

    PubMed  CAS  Google Scholar 

  • Sousa M, Parodi AJ (1995) The molecular basis for the recognition of misfolded glycoproteins by the UDPGlc: glycoprotein glucosyltransferase. EMBO J 14:4196–4203

    PubMed  CAS  Google Scholar 

  • Southwood C, Gow A (2001) Molecular pathways of oligodendrocyte apoptosis revealed by mutations in the proteolipid protein gene. Microsc Res Tech 52:700–708

    PubMed  CAS  Google Scholar 

  • Spiess M (1995) Heads or tails—what determines the orientation of proteins in the membrane FEBS Lett 369:76–79

    PubMed  CAS  Google Scholar 

  • Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT (1997) Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 17:338–340

    PubMed  CAS  Google Scholar 

  • Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT (2000) Spectrum of mutations in long-QT syndrome genes KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 102:1178–1185

    PubMed  CAS  Google Scholar 

  • Spodsberg N, Jacob R, Alfalah M, Zimmer KP, Naim HY (2001) Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder. J Biol Chem 276:23506–23510

    PubMed  CAS  Google Scholar 

  • Springer S, Schekman R (1998) Nucleation of COPII vesicular coat complex by endoplasmic reticulum to Golgi vesicle SNAREs. Science 281:698–700

    PubMed  CAS  Google Scholar 

  • Springer S, Spang A, Schekman R (1999) A primer on vesicle budding. Cell 97:145–148

    PubMed  CAS  Google Scholar 

  • Spritz RA, Strunk KM, Giebel LB, King RA (1990) Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med 332:1724–1728

    Article  Google Scholar 

  • Stockklausner C, Ludwig J, Ruppersberg JP, Klocker N (2001) A sequence motif responsible for ER export and surface expression of Kir20 inward rectifier K+ channels. FEBS Lett 493:129–133

    PubMed  CAS  Google Scholar 

  • Sung CH, Makino C, Baylor D, Nathans J (1994) A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa results in a protein that is defective in localization to the photoreceptor outer segment. J Neurosci 14:5818–5833

    PubMed  CAS  Google Scholar 

  • Tam BM, Moritz OL, Hurd LB, Papermaster DS (2000) Identification of an outer segment targeting signal in the COOH terminus of rhodopsin using transgenic Xenopus laevis. J Cell Biol 151:1369–1380

    PubMed  CAS  Google Scholar 

  • Tamarappoo BK, Verkman AS (1998) Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones. J Clin Invest 15:2257–2267

    Google Scholar 

  • Tamarappoo BK, Yang B, Verkman AS (1999) Misfolding of mutant aquaporin-2 water channels in nephrogenic diabetes insipidus. J Biol Chem 274:34825–34831

    PubMed  CAS  Google Scholar 

  • Thomson CE, Montague P, Jung M, Nave KA, Griffiths IR (1997) Phenotypic severity of murine Plp mutants reflects in vivo and in vitro variations in transport of PLP isoproteins. Glia 20:322–332

    PubMed  CAS  Google Scholar 

  • Tobler AR, Notterpek L, Naef R, Taylor V, Suter U, Shooter EM (1999) Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. J Neurosci 19:2027–2036

    PubMed  CAS  Google Scholar 

  • Towbin JA, Wang Z, Li H (2001) Genotype and severity of long QT syndrome. Drug Metab Dispos 29, 574–579

    PubMed  CAS  Google Scholar 

  • Toyofuku K, Wada I, Valencia JC, Kushimoto T, Ferrans VJ, Hearing VJ (2001a) Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. FASEB J 15:2149–2161

    PubMed  CAS  Google Scholar 

  • Toyofuku K, Wada I, Spritz RA, Hearing VJ (2001b) The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochem J 355: 259–269

    PubMed  CAS  Google Scholar 

  • Treem WR (1995) Congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr 21:1–14

    Article  PubMed  CAS  Google Scholar 

  • Trombetta SE, Parodi AJ (1992) Purification to apparent homogeneity and partial characterization of rat liver UDP-glucose:glycoprotein glucosyltransferase. J Biol Chem 267:9236–9240

    PubMed  CAS  Google Scholar 

  • Trombetta ES, Helenius A (1998) Lectins as chaperones in glycoprotein folding. Curr Opin Struct Biol 8: 587–592

    PubMed  CAS  Google Scholar 

  • Tu L, Wang J, Helm A, Skach WR, Deutsch C (2000) Transmembrane biogenesis of Kv13. Biochemistry 39: 824–36

    PubMed  CAS  Google Scholar 

  • Unson CG, Cypess AM, Kim HN, Goldsmith PK, Carruthers CJ, Merrifield RB, Sakmar TP (1995) Characterization of deletion and truncation mutants of the rat glucagon receptor Seven transmembrane segments are necessary for receptor transport to the plasma membrane and glucagon binding. J Biol Chem 270:27720–27727

    PubMed  CAS  Google Scholar 

  • van den Berg B, Clemons WM Jr, Collinson I, Modis Y, Hartmann E, Harrison SC, Rapoport TA (2004) Xray structure of a protein-conducting channel Nature 427:36–44

    PubMed  Google Scholar 

  • van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (1992) Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nat Genet 2:99–102

    PubMed  Google Scholar 

  • van Klompenburg W, Nilsson I, von Heijne G, de Kruijff B (1997) Anionic phospholipids are determinants of membrane protein topology. EMBO J 16:4261–4266

    PubMed  Google Scholar 

  • van Leeuwen JE, Kearse KP (1996) The related molecular chaperones calnexin and calreticulin differentially associate with nascent T cell antigen receptor proteins within the endoplasmic reticulum. J Biol Chem 271: 25345–25349

    PubMed  Google Scholar 

  • van Soest S, Westerveld A, de Jong PT, Bleeker-Wagemakers EM, Bergen AA (1999) Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol 43:321–334

    PubMed  Google Scholar 

  • Verkman AS, Mitra AK (2000) Structure and function of aquaporin water channels. Am J Physiol Renal Physiol 278:F13–28

    PubMed  CAS  Google Scholar 

  • von Heijne G, Gavel Y (1988) Topogenic signals in integral membrane proteins Eur J Biochem 174: 671–678

    Google Scholar 

  • von Heijne G (1994) Membrane proteins: from sequence to structure. Annu Rev Biophys Biomol Struct 23: 167–192

    Google Scholar 

  • Votsmeier C, Gallwitz D (2001) An acidic sequence of a putative yeast Golgi membrane protein binds COPII and facilitates ER export. EMBO J 20:6742–50

    PubMed  CAS  Google Scholar 

  • Waheed A, Parkkila S, Saarnio J, Fleming RE, Zhou XY, Tomatsu S, Britton RS, Bacon BR, Sly WS (1999) Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci USA 96, 1579–1584

    PubMed  CAS  Google Scholar 

  • Waheed A, Parkkila S, Zhou XY, Tomatsu S, Tsuchihashi Z, Feder JN, Schatzman RC, Britton RS, Bacon BR, Sly WS (1997) Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with β 2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci USA 94:12384–12389

    PubMed  CAS  Google Scholar 

  • Wallin E, von Heijne G (1995) Properties of N-terminal tails in G-protein coupled receptors: a statistical study. Protein Eng 8:693–698

    PubMed  CAS  Google Scholar 

  • Walter P, Blobel G (1981) Translocation of proteins across the endoplasmic reticulum III Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J Cell Biol 91:557–61

    PubMed  CAS  Google Scholar 

  • Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Toubin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 12:17–23

    PubMed  Google Scholar 

  • Wessels HP, Spiess M (1988) Insertion of a multispanning membrane protein occurs sequentially and requires only one signal sequence. Cell 55:61–70

    PubMed  CAS  Google Scholar 

  • White TW (2000) Functional analysis of human Cx26 mutations associated with deafness. Brain Res Rev 32: 181–183

    PubMed  CAS  Google Scholar 

  • Wieland FT, Gleason ML, Serafini TA, Rothman JE (1987) The rate of bulk flow from the endoplasmic reticulum to the cell surface. Cell 50:289–300

    PubMed  CAS  Google Scholar 

  • Wojcik J, Berg MA, Esposito N, Geffner ME, Sakati N, Reiter EO, Dower S, Francke U, Postel-Vinay MC, Finidori J (1998) Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. J Clin Endocrinol Metab 83: 4481–4489

    PubMed  CAS  Google Scholar 

  • Woods KA, Dastot F, Preece MA, Clark AJ, Postel-Vinay MC, Chatelain PG, Ranke MB, Rosenfeld RG, Amselem S, Savage MO (1997) Phenotype:genotype relationships in growth hormone insensitivity syndrome. J Clin Endocrinol Metab 82:3529–3535

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Fujii R, Toyofuku Y, Saito T, Koseki H, Hsu VW, Aoe T (2001) The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum. EMBO J 20:3082–3091

    PubMed  CAS  Google Scholar 

  • Yamashita F, Horie M, Kubota T, Yoshida H, Yumoto Y, Kobori A, Ninomiya T, Kono Y, Haruna T, Tsuji K, Washizuka T, Takano M, Otani H, Sasayama S, Aizawa Y (2001) Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus. J Mol Cell Cardiol 33:197–207

    PubMed  CAS  Google Scholar 

  • Yang Y, Janich S, Cohn JA, Wilson JM (1993) The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc Nat Acad Sci 90: 9480–9484

    PubMed  CAS  Google Scholar 

  • Yeaman C, Grindstaff KK, Nelson J (1999) New perspectives on mechanisms involved in generating epithelial polarity. Physiol Rev 79:73–97

    PubMed  CAS  Google Scholar 

  • Yokoyama K, Yamauchi A, Izumi M, Itoh T, Ando A, Imai E, Kamada T, Ueda N (1996) A low-affinity vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 7:410–414

    PubMed  CAS  Google Scholar 

  • Young P, Suter U (2001) Disease mechanisms and potential therapeutic strategies in Charcot-Marie-Tooth disease. Brain Res Brain Res Rev 36:213–221

    PubMed  CAS  Google Scholar 

  • Yuan H, Michelsen K, Schwappach B (2003) 14-3-3 dimers probe the assembly status of multimeric membrane proteins. Curr Biol 13:638–646

    PubMed  CAS  Google Scholar 

  • Zeitlin PL (2000) Future pharmacological treatment of cystic fibrosis. Respiration 67:351–357

    PubMed  CAS  Google Scholar 

  • Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane KATP channels. Neuron 22:537–48

    PubMed  CAS  Google Scholar 

  • Zielenski J (2000) Genotype and phenotype in cystic fibrosis. Respiration 67:117–133

    PubMed  CAS  Google Scholar 

  • Zhang JX, Braakman I, Matlack KE, Helenius A (1997) Quality control in the secretory pathway: the role of calreticulin, calnexin and BiP in the retention of glycoproteins with C-terminal truncations. Mol Biol Cell 8: 1943–1954

    PubMed  CAS  Google Scholar 

  • Zhou Z, Gong Q, Epstein ML, January CT (1998) HERG channel dysfunction in human long QT syndrome Intracellular transport and functional defects. J Biol Chem 273:21061–21066

    PubMed  CAS  Google Scholar 

  • Zhou Z, Gong Q, January CT (1999) Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome Pharmacological and temperature effects. J Biol Chem 274:31123–31126

    PubMed  CAS  Google Scholar 

  • Zuccon L, Corsi B, Levi S, Mattioli M, Fracanzani AL, Corti A, Albertini A, Sampietro M, Fargion S, Arosio P (2000) Immunohistochemistry of HFE in the duodenum of C282Y homozygotes with antisera for recombinant HFE protein. Haematologica 85:346–351

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str.10, 13125, Berlin, Germany

    R. Schülein

Authors
  1. R. Schülein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Schülein .

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag

About this chapter

Cite this chapter

Schülein, R. (2004). The early stages of the intracellular transport of membrane proteins: clinical and pharmacological implications. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 151. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-004-0022-8

Download citation

  • DOI: https://doi.org/10.1007/s10254-004-0022-8

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-22096-1

  • Online ISBN: 978-3-540-44423-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation