Skip to main content

Advertisement

SpringerLink
Log in

The Very Large G Protein Coupled Receptor (Vlgr1) in Hair Cells

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The very large G protein coupled receptor (Vlgr1) is a member of adhesion receptors or large N-terminal family B-7 transmembrane helixes (LNB7TM) receptors within the seven trans-membrane receptor superfamily. Vlgr1 is the largest GPCR identified to date; its mRNA spans 19 kb and encodes 6,300 amino acids. Vlgr1 is a core component of ankle-link complex in inner ear hair cells. Knock-out and mutation mouse models show that loss of Vlgr1 function leads to abnormal stereociliary development and hearing loss, indicating crucial roles of Vlgr1 in hearing transduction or auditory system development. Over the past 10 or so years, human genetics data suggested that Vlgr1 mutations cause Usher syndromes and seizures. Although significant progresses have been made, the details of Vlgr1’s function in hair cells, its signaling cascade, and the mechanisms underlying causative effects of Vlgr1 mutations in human diseases remain elusive and ask for further investigation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alonso-Garcia N, Ingles-Prieto A, Sonnenberg A, de Pereda JM (2009) Structure of the Calx-beta domain of the integrin beta4 subunit: insights into function and cation-independent stability. Acta Crystallogr D: Biol Crystallogr 65:858–871

    Article  Google Scholar 

  • Arac D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Sudhof TC, Brunger AT (2012) A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J 31:1364–1378

    Article  PubMed  CAS  Google Scholar 

  • Assad JA, Shepherd GM, Corey DP (1991) Tip-link integrity and mechanical transduction in vertebrate hair cells. Neuron 7:985–994

    Article  PubMed  CAS  Google Scholar 

  • Besnard T, Vache C, Baux D, Larrieu L, Abadie C, Blanchet C, Odent S, Blanchet P, Calvas P, Hamel C et al (2012) Non-USH2A mutations in USH2 patients. Hum Mutat 33:504–510

    Article  PubMed  CAS  Google Scholar 

  • Blanchet C, Erostegui C, Sugasawa M, Dulon D (1996) Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors. J Neurosci 16:2574–2584

    PubMed  CAS  Google Scholar 

  • Bolliger MF, Martinelli DC, Sudhof TC (2011) The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc Natl Acad Sci U S A 108:2534–2539

    Article  PubMed  CAS  Google Scholar 

  • Bonnet C, El-Amraoui A (2012) Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches. Curr Opin Neurol 25:42–49

    Article  PubMed  CAS  Google Scholar 

  • Bonnet C, Grati M, Marlin S, Levilliers J, Hardelin JP, Parodi M, Niasme-Grare M, Zelenika D, Delepine M, Feldmann D et al (2011) Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. Orphanet J Rare Dis 6:21

    Article  PubMed  Google Scholar 

  • Chabrol E, Navarro V, Provenzano G, Cohen I, Dinocourt C, Rivaud-Pechoux S, Fricker D, Baulac M, Miles R, Leguern E et al (2010) Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1-deficient mice. Brain 133:2749–2762

    Article  PubMed  Google Scholar 

  • Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AG (2011) Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol 12:455–469

    Article  PubMed  Google Scholar 

  • Chai R, Kuo B, Wang T, Liaw EJ, Xia A, Jan TA, Liu Z, Taketo MM, Oghalai JS, Nusse R et al (2012) Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci U S A 109:8167–8172

    Article  PubMed  CAS  Google Scholar 

  • Cook JV, Eidne KA (1997) An intramolecular disulfide bond between conserved extracellular cysteines in the gonadotropin-releasing hormone receptor is essential for binding and activation. Endocrinology 138:2800–2806

    Article  PubMed  CAS  Google Scholar 

  • Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, Henderson DJ, Spurr N, Stanier P, Fisher EM et al (2003) Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol 13:1129–1133

    Article  PubMed  CAS  Google Scholar 

  • de Pereda JM, Ortega E, Alonso-Garcia N, Gomez-Hernandez M, Sonnenberg A (2009) Advances and perspectives of the architecture of hemidesmosomes: lessons from structural biology. Cell Adh Migr 3:361–364

    Article  PubMed  Google Scholar 

  • Delmaghani S, Aghaie A, Michalski N, Bonnet C, Weil D, Petit C (2012) Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness. Hum Mol Genet 21:3835–3844

    Google Scholar 

  • DeWire SM, Kim J, Whalen EJ, Ahn S, Chen M, Lefkowitz RJ (2008) Beta-arrestin-mediated signaling regulates protein synthesis. J Biol Chem 283:10611–10620

    Article  PubMed  CAS  Google Scholar 

  • Dong JH, Chen X, Cui M, Yu X, Pang Q, Sun JP (2012) Beta2-adrenergic receptor and astrocyte glucose metabolism. J Mol Neurosci 48:456–463

    Article  PubMed  CAS  Google Scholar 

  • Drescher MJ, Khan KM, Beisel KW, Karadaghy AA, Hatfield JS, Kim SY, Drescher AJ, Lasak JM, Barretto RL, Shakir AH et al (1997) Expression of adenylyl cyclase type I in cochlear inner hair cells. Brain Res Mol Brain Res 45:325–330

    Article  PubMed  CAS  Google Scholar 

  • Ebermann I, Scholl HP, Charbel Issa P, Becirovic E, Lamprecht J, Jurklies B, Millan JM, Aller E, Mitter D, Bolz H (2007) A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss. Hum Genet 121:203–211

    Article  PubMed  CAS  Google Scholar 

  • Ebermann I, Wiesen MH, Zrenner E, Lopez I, Pigeon R, Kohl S, Lowenheim H, Koenekoop RK, Bolz HJ (2009) GPR98 mutations cause Usher syndrome type 2 in males. J Med Genet 46:277–280

    Article  PubMed  CAS  Google Scholar 

  • Ebermann I, Phillips JB, Liebau MC, Koenekoop RK, Schermer B, Lopez I, Schafer E, Roux AF, Dafinger C, Bernd A et al (2010) PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome. J Clin Invest 120:1812–1823

    Article  PubMed  CAS  Google Scholar 

  • Eudy JD, Weston MD, Yao S, Hoover DM, Rehm HL, Ma-Edmonds M, Yan D, Ahmad I, Cheng JJ, Ayuso C et al (1998) Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science 280:1753–1757

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Busquets X, Kornig A, Bucior I, Burger MM, Anselmetti D (2009) Self-recognition and Ca2+ —dependent carbohydrate-carbohydrate cell adhesion provide clues to the cambrian explosion. Mol Biol Evol 26:2551–2561

    Article  PubMed  CAS  Google Scholar 

  • Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256–1272

    Article  PubMed  CAS  Google Scholar 

  • Fukata Y, Lovero KL, Iwanaga T, Watanabe A, Yokoi N, Tabuchi K, Shigemoto R, Nicoll RA, Fukata M (2010) Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A 107:3799–3804

    Article  PubMed  CAS  Google Scholar 

  • Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson CD, Wang S, Eckhardt AE, Cowan CL, Spurney RF, Luttrell LM et al (2006) Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem 281:10856–10864

    Article  PubMed  CAS  Google Scholar 

  • Goodyear R, Richardson G (1999) The ankle-link antigen: an epitope sensitive to calcium chelation associated with the hair-cell surface and the calycal processes of photoreceptors. J Neurosci 19:3761–3772

    PubMed  CAS  Google Scholar 

  • Goodyear RJ, Marcotti W, Kros CJ, Richardson GP (2005) Development and properties of stereociliary link types in hair cells of the mouse cochlea. J Comp Neurol 485:75–85

    Article  PubMed  Google Scholar 

  • Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett 586:1214–1219

    Article  PubMed  CAS  Google Scholar 

  • Hall TM, Porter JA, Beachy PA, Leahy DJ (1995) A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of Sonic hedgehog. Nature 378:212–216

    Article  PubMed  CAS  Google Scholar 

  • Hamann J, Vogel B, van Schijndel GM, van Lier RA (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184:1185–1189

    Article  PubMed  CAS  Google Scholar 

  • Hara MR, Kovacs JJ, Whalen EJ, Rajagopal S, Strachan RT, Grant W, Towers AJ, Williams B, Lam CM, Xiao K et al (2011) A stress response pathway regulates DNA damage through beta2-adrenoreceptors and beta-arrestin-1. Nature 477:349–353

    Article  PubMed  CAS  Google Scholar 

  • Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809

    Article  PubMed  CAS  Google Scholar 

  • He DZ, Dallos P (1999) Development of acetylcholine-induced responses in neonatal gerbil outer hair cells. J Neurophysiol 81:1162–1170

    PubMed  CAS  Google Scholar 

  • Hilgert N (2009) Novel human pathological mutations. Gene symbol: GPR98. Disease: Usher syndrome 2C. Hum Genet 125:342

    PubMed  Google Scholar 

  • Hilgert N, Kahrizi K, Dieltjens N, Bazazzadegan N, Najmabadi H, Smith RJ, Van Camp G (2009) A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. J Med Genet 46:272–276

    Article  PubMed  CAS  Google Scholar 

  • Hmani-Aifa M, Benzina Z, Zulfiqar F, Dhouib H, Shahzadi A, Ghorbel A, Rebai A, Soderkvist P, Riazuddin S, Kimberling WJ et al (2009) Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family. Eur J Hum Genet 17:474–482

    Article  PubMed  CAS  Google Scholar 

  • Huang LC, Thorne PR, Vlajkovic SM, Housley GD (2010) Differential expression of P2Y receptors in the rat cochlea during development. Purinergic Signal 6:231–248

    Article  PubMed  CAS  Google Scholar 

  • Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW et al (2012) Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol 32:1408–1420

    Article  PubMed  CAS  Google Scholar 

  • Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H (2008) Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem 283:14469–14478

    Article  PubMed  CAS  Google Scholar 

  • Jagger DJ, Ashmore JF (1999) Regulation of ionic currents by protein kinase A and intracellular calcium in outer hair cells isolated from the guinea-pig cochlea. Pflugers Arch 437:409–416

    Article  PubMed  CAS  Google Scholar 

  • Johnson KR, Zheng QY, Weston MD, Ptacek LJ, Noben-Trauth K (2005) The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics 85:582–590

    Article  PubMed  CAS  Google Scholar 

  • Kakehata S, Nakagawa T, Takasaka T, Akaike N (1993) Cellular mechanism of acetylcholine-induced response in dissociated outer hair cells of guinea-pig cochlea. J Physiol 463:227–244

    PubMed  CAS  Google Scholar 

  • Kalachikov S, Evgrafov O, Ross B, Winawer M, Barker-Cummings C, Martinelli Boneschi F, Choi C, Morozov P, Das K, Teplitskaya E et al (2002) Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 30:335–341

    Article  PubMed  Google Scholar 

  • Klein BD, Fu YH, Ptacek LJ, White HS (2005) Auditory deficits associated with the frings mgr1 (mass1) mutation in mice. Dev Neurosci 27:321–332

    Article  PubMed  CAS  Google Scholar 

  • Kleyman TR, Carattino MD, Hughey RP (2009) ENaC at the cutting edge: regulation of epithelial sodium channels by proteases. J Biol Chem 284:20447–20451

    Article  PubMed  CAS  Google Scholar 

  • Kojro E, Fahrenholz F (1995) Ligand-induced cleavage of the V2 vasopressin receptor by a plasma membrane metalloproteinase. J Biol Chem 270:6476–6481

    Article  PubMed  CAS  Google Scholar 

  • Kowalik L, Hudspeth AJ (2011) A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick’s cochlea. Dev Biol 354:221–231

    Article  PubMed  CAS  Google Scholar 

  • Kumagami H, Beitz E, Wild K, Zenner HP, Ruppersberg JP, Schultz JE (1999) Expression pattern of adenylyl cyclase isoforms in the inner ear of the rat by RT-PCR and immunochemical localization of calcineurin in the organ of Corti. Hear Res 132:69–75

    Article  PubMed  CAS  Google Scholar 

  • Kussel-Andermann P, El-Amraoui A, Safieddine S, Hardelin JP, Nouaille S, Camonis J, Petit C (2000) Unconventional myosin VIIA is a novel A-kinase-anchoring protein. J Biol Chem 275:29654–29659

    Article  PubMed  CAS  Google Scholar 

  • Lagerstrom MC, Schioth HB (2008) Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 7:339–357

    Article  PubMed  Google Scholar 

  • Lee JJ, Ekker SC, von Kessler DP, Porter JA, Sun BI, Beachy PA (1994) Autoproteolysis in hedgehog protein biogenesis. Science 266:1528–1537

    Article  PubMed  CAS  Google Scholar 

  • Lefkowitz RJ, Sun JP, Shukla AK (2008) A crystal clear view of the beta2-adrenergic receptor. Nat Biotechnol 26:189–191

    Article  PubMed  CAS  Google Scholar 

  • Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF, Ushkaryov YA (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem 272:21504–21508

    Article  PubMed  CAS  Google Scholar 

  • Limviphuvadh V, Chua LL, Eisenhaber F, Adhikari S, Maurer-Stroh S (2010a) Is LGI2 the candidate gene for partial epilepsy with pericentral spikes? J Bioinform Comput Biol 8:117–127

    Article  PubMed  CAS  Google Scholar 

  • Limviphuvadh V, Chua LL, Rahim RA, Eisenhaber F, Maurer-Stroh S, Adhikari S (2010b) Similarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2. BMC Biochem 11:39

    Article  PubMed  Google Scholar 

  • Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S (2004) Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J Biol Chem 279:31823–31832

    Article  PubMed  CAS  Google Scholar 

  • Little KD, Hemler ME, Stipp CS (2004) Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 15:2375–2387

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Marnell LL, Marjon KD, Mold C, Du Clos TW, Sun PD (2008) Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature 456:989–992

    Article  PubMed  CAS  Google Scholar 

  • McGee J, Goodyear RJ, McMillan DR, Stauffer EA, Holt JR, Locke KG, Birch DG, Legan PK, White PC, Walsh EJ et al (2006) The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles. J Neurosci 26:6543–6553

    Article  PubMed  CAS  Google Scholar 

  • McMillan DR, White PC (2004) Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol Cell Neurosci 26:322–329

    Article  PubMed  CAS  Google Scholar 

  • McMillan DR, White PC (2010) Studies on the very large G protein-coupled receptor: from initial discovery to determining its role in sensorineural deafness in higher animals. Adv Exp Med Biol 706:76–86

    Article  PubMed  CAS  Google Scholar 

  • McMillan DR, Kayes-Wandover KM, Richardson JA, White PC (2002) Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J Biol Chem 277:785–792

    Article  PubMed  CAS  Google Scholar 

  • Michalski N, Michel V, Bahloul A, Lefevre G, Barral J, Yagi H, Chardenoux S, Weil D, Martin P, Hardelin JP et al (2007) Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci 27:6478–6488

    Article  PubMed  CAS  Google Scholar 

  • Mikolajek H, Kolstoe SE, Pye VE, Mangione P, Pepys MB, Wood SP (2011) Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component. J Mol Recognit 24:371–377

    Article  PubMed  CAS  Google Scholar 

  • Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Saenz A, Poza JJ, Galan J, Gesk S, Sarafidou T, Mautner VF, Binelli S et al (2002) Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119–1128

    Article  PubMed  CAS  Google Scholar 

  • Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, Matsui A, Arinami T, Ptacek LJ (2002) A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol 52:654–657

    Article  PubMed  CAS  Google Scholar 

  • Nelson CD, Kovacs JJ, Nobles KN, Whalen EJ, Lefkowitz RJ (2008) Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor. J Biol Chem 283:21093–21101

    Article  PubMed  CAS  Google Scholar 

  • Nikkila H, McMillan DR, Nunez BS, Pascoe L, Curnow KM, White PC (2000) Sequence similarities between a novel putative G protein-coupled receptor and Na+/Ca2+ exchangers define a cation binding domain. Mol Endocrinol 14:1351–1364

    Article  PubMed  CAS  Google Scholar 

  • Paavola KJ, Hall RA (2012) Adhesion G Protein-Coupled Receptors: Signaling, Pharmacology & Mechanisms of Activation. Mol Pharmacol 82:777–783

    Google Scholar 

  • Paavola KJ, Stephenson JR, Ritter SL, Alter SP, Hall RA (2011) The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity. J Biol Chem 286:28914–28921

    Article  PubMed  CAS  Google Scholar 

  • Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL, Mandell JW, Ravichandran KS (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434

    Article  PubMed  CAS  Google Scholar 

  • Perler FB (1998) Protein splicing of inteins and hedgehog autoproteolysis: structure, function, and evolution. Cell 92:1–4

    Article  PubMed  CAS  Google Scholar 

  • Porter JA, von Kessler DP, Ekker SC, Young KE, Lee JJ, Moses K, Beachy PA (1995) The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature 374:363–366

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D et al (2011) Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477:549–555

    Article  PubMed  CAS  Google Scholar 

  • Reiners J, van Wijk E, Marker T, Zimmermann U, Jurgens K, te Brinke H, Overlack N, Roepman R, Knipper M, Kremer H et al (2005) Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum Mol Genet 14:3933–3943

    Article  PubMed  CAS  Google Scholar 

  • Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC et al (2007) GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318:1266–1273

    Article  PubMed  CAS  Google Scholar 

  • Scheel H, Tomiuk S, Hofmann K (2002) A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet 11:1757–1762

    Article  PubMed  CAS  Google Scholar 

  • Schioth HB, Fredriksson R (2005) The GRAFS classification system of G-protein coupled receptors in comparative perspective. Gen Comp Endocrinol 142:94–101

    Article  PubMed  Google Scholar 

  • Seppala EH, Jokinen TS, Fukata M, Fukata Y, Webster MT, Karlsson EK, Kilpinen SK, Steffen F, Dietschi E, Leeb T et al (2011) LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet 7:e1002194

    Article  PubMed  CAS  Google Scholar 

  • Shi F, Kempfle JS, Edge AS (2012) Wnt-responsive lgr5-expressing stem cells are hair cell progenitors in the cochlea. J Neurosci 32:9639–9648

    Article  PubMed  CAS  Google Scholar 

  • Shukla AK, Sun JP, Lefkowitz RJ (2008) Crystallizing thinking about the beta2-adrenergic receptor. Mol Pharmacol 73:1333–1338

    Article  PubMed  CAS  Google Scholar 

  • Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptacek LJ (2001) A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron 31:537–544

    Article  PubMed  CAS  Google Scholar 

  • Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102:2916–2924

    Article  PubMed  CAS  Google Scholar 

  • Szonyi M, Csermely P, Sziklai I (1999) Acetylcholine-induced phosphorylation in isolated outer hair cells. Acta Otolaryngol 119:185–188

    Article  PubMed  CAS  Google Scholar 

  • van Wijk E, van der Zwaag B, Peters T, Zimmermann U, Te Brinke H, Kersten FF, Marker T, Aller E, Hoefsloot LH, Cremers CW et al (2006) The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum Mol Genet 15:751–765

    Article  PubMed  Google Scholar 

  • Vlajkovic SM, Abi S, Wang CJ, Housley GD, Thorne PR (2007) Differential distribution of adenosine receptors in rat cochlea. Cell Tissue Res 328:461–471

    Article  PubMed  CAS  Google Scholar 

  • Vlajkovic SM, Housley GD, Thorne PR (2009) Adenosine and the auditory system. Curr Neuropharmacol 7:246–256

    Article  PubMed  CAS  Google Scholar 

  • Weston MD, Luijendijk MW, Humphrey KD, Moller C, Kimberling WJ (2004) Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet 74:357–366

    Article  PubMed  CAS  Google Scholar 

  • Wu M, Le HD, Wang M, Yurkov V, Omelchenko A, Hnatowich M, Nix J, Hryshko LV, Zheng L (2010) Crystal structures of progressive Ca2+ binding states of the Ca2+ sensor Ca2+ binding domain 1 (CBD1) from the CALX Na+/Ca2+ exchanger reveal incremental conformational transitions. J Biol Chem 285:2554–2561

    Article  PubMed  CAS  Google Scholar 

  • Xiao K, Sun J, Kim J, Rajagopal S, Zhai B, Villen J, Haas W, Kovacs JJ, Shukla AK, Hara MR et al (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci U S A 107:15299–15304

    Article  PubMed  CAS  Google Scholar 

  • Xu L, Begum S, Hearn JD, Hynes RO (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A 103:9023–9028

    Article  PubMed  CAS  Google Scholar 

  • Yagi H, Takamura Y, Yoneda T, Konno D, Akagi Y, Yoshida K, Sato M (2005) Vlgr1 knockout mice show audiogenic seizure susceptibility. J Neurochem 92:191–202

    Article  PubMed  CAS  Google Scholar 

  • Yagi H, Tokano H, Maeda M, Takabayashi T, Nagano T, Kiyama H, Fujieda S, Kitamura K, Sato M (2007) Vlgr1 is required for proper stereocilia maturation of cochlear hair cells. Genes Cells 12:235–250

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Liu X, Zhao Y, Adamian M, Pawlyk B, Sun X, McMillan DR, Liberman MC, Li T (2010) Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet 6:e1000955

    Article  PubMed  Google Scholar 

  • Yu YE, Wen L, Silva J, Li Z, Head K, Sossey-Alaoui K, Pao A, Mei L, Cowell JK (2010) Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Hum Mol Genet 19:1702–1711

    Article  PubMed  CAS  Google Scholar 

  • Zallocchi M, Delimont D, Meehan DT, Cosgrove D (2012a) Regulated Vesicular Trafficking of Specific PCDH15 and VLGR1 Variants in Auditory Hair Cells. J Neurosci 32:13841–13859

    Article  PubMed  CAS  Google Scholar 

  • Zallocchi M, Meehan DT, Delimont D, Rutledge J, Gratton MA, Flannery J, Cosgrove D (2012b) Role for a novel Usher protein complex in hair cell synaptic maturation. PLoS One 7:e30573

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Basic Research Program of China (973; 2012CB910402 to J.S., 2011CB504505 to Z.X.), National Natural Science Foundation of China (31070969 to Z.X. and 31100580, 31271505 to J.S.), Specialized Research Fund for the Doctoral Program of Higher Education (20100131110014 to Z.X.), Foundation for Excellent Young and Middle-Aged Scientists of Shandong Province, China (BS2011SW020 to J.S, BS2010SW017 to Z.X.), Interdiscipline Fund of Shandong University (2012JC021 to Z.X.), and Independence Innovation Foundation of Shandong University (2012TS114 to J.S.).

Author information

Authors and Affiliations

  1. Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan, Shandong, China

    Jin-Peng Sun, Rong Li, Hong-Ze Ren, Xiao Yu & Zhi-Gang Xu

  2. Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, China

    Hong-Ze Ren & Zhi-Gang Xu

  3. Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, China

    Jin-Peng Sun & Rong Li

  4. Shandong Provincial Hospital, Jinan, Shandong, China

    Jin-Peng Sun & Rong Li

  5. Qilu Hospital, Jinan, Shandong, China

    An-Ting Xu

  6. Department of Physiology, School of Medicine, Shandong University, Jinan, Shandong, China

    Xiao Yu

Authors
  1. Jin-Peng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong-Ze Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. An-Ting Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi-Gang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jin-Peng Sun or Zhi-Gang Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, JP., Li, R., Ren, HZ. et al. The Very Large G Protein Coupled Receptor (Vlgr1) in Hair Cells. J Mol Neurosci 50, 204–214 (2013). https://doi.org/10.1007/s12031-012-9911-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-012-9911-5

Keywords

Search

Navigation