Skip to main content
SpringerLink
Log in

Annexins and their interacting proteins in membrane traffic

  • Published:
Protoplasma Aims and scope Submit manuscript

Summary

Annexins are calcium-binding proteins which share common properties due to their homologous core domain. This domain binds phospholipids in a Ca2+-dependent manner. Although extensively studied over 20 years, the function of annexins remains to be elucidated. They are proposed to participate in calcium homeostasis and in the regulation of ion-channel activities, and evidence is accumulating for their role in membrane traffic. Their function is likely to be mediated by their interactions with other proteins such as S100 proteins, C2-domain-containing molecules, and cytoskeletal elements. This review discusses experiments performed in a cellular context, arguing for annexin involvement in exocytosis and endocytosis.

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

Similar content being viewed by others

Abbreviations

cPLA2:

cytosolic phospholipase A2

GAP:

GTPase activation protein

NSF:

N-ethylmaleimide sensitive factor

PIP2:

phosphatidylinositol 4,5-biphosphate

PKC:

protein kinase C

PLC:

phospholipase C

PI3K:

phosphatidylinositol-3 kinase

SNAP:

soluble NSF-associated protein

SNARE:

soluble NSF-associated receptor

References

  • Ali SM, Burgoyne RD (1990) The stimulatory effect of calpactin (annexin II) on calcium-dependent exocytosis in chromaffin cells: requirement for both the N-terminal and core domains of p36 and ATP. Cell Signal 2: 265–276

    Google Scholar 

  • —, Geisow MJ, Burgoyne RD (1989) A role for calpactin in calcium-dependent exocytosis in adrenal chromaffin cells. Nature 340: 313–315

    Google Scholar 

  • Bandorowicz-Pikula J (1998) A nucleotide-binding domain of porcine liver annexin VI. Mol Cell Biochem 181: 11–20

    Google Scholar 

  • Barbieri MA, Roberts RL, Mukhopadhyay A, Stahl PD (1996) Rab5 regulates the dynamics of early endosome fusion. Biocell 20: 331–338

    Google Scholar 

  • Beckers CJM, Block MR, Glick BS, Rothman JE, Balch WE (1989) Vesicular transport between the endoplasmic reticulum and the Golgi stack requires the NEM-sensitive fusion protein. Nature 339: 397–398

    Google Scholar 

  • Brown DA, London E (1997) Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem Biophys Res Commun 240: 1–7

    Google Scholar 

  • Burgoyne RD, Morgan A (1998) Analysis of regulated exocytosis in adrenal chromaffin cells: insights into NSF/SNAP/SNARE function. Bioessays 20: 328–335

    Google Scholar 

  • Cardone M, Mostov K (1995) Wortmannin inhibits transcytosis of dimeric IgA by the polymeric immunoglobulin receptor. FEBS Lett 376: 74–76

    Google Scholar 

  • —, Smith BL, Song W, Mochly-Rosen D, Mostov KE (1994) Phorbol myristate acetate-mediated stimulation of transcytosis and apical recycling in MDCK cells. J Cell Biol 124: 717–727

    Google Scholar 

  • Carroll AD, Moyen C, Kesteren PV, Tooke F, Battley NH, Brownlee C (1998) Calcium, annexins, and GTP modulate exocytosis from maize root cap protoplasts. Plant Cell 10: 1267–1276

    Google Scholar 

  • Carter LL (1993) Multiple GTP-binding proteins participate in clathrin-coated vesicle-mediated endocytosis. J Cell Biol 120: 37–45

    Google Scholar 

  • Chasserot GS, Vitale N, Sagot I, Delouche B, Dirrig S, Pradel LA, Henry JP, Aunis D, Bader MF (1996) Annexin II in exocytosis: catecholamine secretion requires the translocation of p36 to the subplasmalemmal region in chromaffin cells. J Cell Biol 133: 1217–1236

    Google Scholar 

  • Chavez RA, Miller SG, Moore HP (1996) A biosynthetic regulated secretory pathway in constitutive secretory cells. J Cell Biol 133: 1177–1191

    Google Scholar 

  • Christmas P, Callaway J, Fallon J, Jones J, Haigier HT (1991) Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland. J Biol Chem 266: 2499–2507

    Google Scholar 

  • Creutz CE (1992) The annexins and exocytosis. Science 258: 924–931

    Google Scholar 

  • Davis AJ, Butt JT, Walker JH, Moss SE, Gawler DJ (1996) The Ca2+-dependent lipid binding domain of P120GAP mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins: evidence for a direct interaction between annexin VI and P120GAP. J Biol Chem 271: 24333–24336

    Google Scholar 

  • de Figueiredo P, Drecktrah D., Katzenellenbogen JA, Strang M, Brown WJ (1998) Evidence that phospholipase A2 activity is required for Golgi complex and trans Golgi network membrane tubulation. Proc Natl Acad Sci USA 95: 8642–8647

    Google Scholar 

  • Delouche B, Pradel LA, Henry JP (1997) Phosphorylation by protein kinase C of annexin 2 in chromaffin cells stimulated by nicotine. J Neurochem 68: 1720–1727

    Google Scholar 

  • De Matteis M, Morrow JS (1998) The role of ankyrin and spectrin in membrane transport and domain formation. Curr Opin Cell Biol 10: 542–549

    Google Scholar 

  • Donnelly SR, Moss SE (1997) Annexins in the secretory pathway. Cell Mol Life Sci 53: 533–538

    Google Scholar 

  • Doring V, Veretout F, Albrecht R, Muhlbauer B, Schlatterer C, Schleicher M, Noegel AA (1995) The in vivo role of annexin VII (synexin): characterization of an annexin VII-deficient Dictyostelium mutant indicates an involvement in Ca2+-regulated processes. J Cell Sci 108: 2065–2076

    Google Scholar 

  • Emans N, Gorvel JP, Walter C, Gerke V, Kellner R, Griffiths G, Gruenberg J (1993) Annexin II is a major component of fusogenic endosomal vesicles. J Cell Biol 120: 1357–1369

    Google Scholar 

  • Fiedler K, Lafont F, Parton RG, Simons K (1995) Annexin XIIIb: a novel epithelial specific annexin is implicated in vesicular traffic to the apical plasma membrane. J Cell Biol 128: 1043–1053

    Google Scholar 

  • Futter CE, Felder S, Schlessinger J, Ullrich A, Hopkins CR (1993) Annexin I phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor. J Cell Biol 120: 77–83

    Google Scholar 

  • Geppert M, Sudhof TC (1998) RAB3 and synaptotagmin: the yin and yang of synaptic membrane fusion. Annu Rev Neurosci 21: 75–95

    Google Scholar 

  • Graham ME, Gerke V, Burgoyne RD (1997) Modification of annexin II expression in PC12 cell lines does not affect Ca2+-dependent exocytosis. Mol Biol Cell 8: 431–442

    Google Scholar 

  • Harder T, Gerke V (1993) The subcellular distribution of early endosomes is affected by the annexin II2p11(2) complex. J Cell Biol 123: 1119–1132

    Google Scholar 

  • — — (1994) The annexin II2p11(2) complex is the major protein component of the Triton X-100-insoluble low-density fraction prepared from MDCK cells in the presence of Ca2+. Biochim Biophys Acta 1223: 375–382

    Google Scholar 

  • —, Kellner R, Parton RG, Gruenberg J (1997) Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol. Mol Biol Cell 8: 533–545

    Google Scholar 

  • Hay JC, Scheller RH (1997) SNAREs and NSF in targeted membrane fusion. Curr Opin Cell Biol 9: 505–512

    Google Scholar 

  • Hu RJ, Bennett V (1991) In vitro proteolysis of brain spectrin by calpain I inhibits association of spectrin with ankyrin-independent membrane binding site(s). J Biol Chem 266: 18200–18205

    Google Scholar 

  • Ikura M (1996) Calcium binding and conformational response in EF-hand proteins. Trends Biol Sci 21: 14–17

    Google Scholar 

  • Jost M, Zeuschner D, Seemann J, Weber K, Gerke V (1997) Identification and characterization of a novel type of annexin-membrane interaction: Ca2+ is not required for the association of annexin II with early endosomes. J Cell Sci 110: 221–228

    Google Scholar 

  • Kaetzel MA, Chan HC, Dubinsky WP, Dedman JR, Nelson DJ (1994) A role for annexin IV in epithelial cell function: inhibition of calcium-activated chloride conductance. J Biol Chem 269: 5297–5302

    Google Scholar 

  • Kamal A, Ying Y, Anderson RG (1998) Annexin VI-mediated loss of spectrin during coated pit budding is coupled to delivery of LDL to lysosomes. J Cell Biol 142: 937–947

    Google Scholar 

  • Konig J, Prenen J, Nilius B, Gerke V (1998) The annexin II-p11 complex is involved in regulated exocytosis in bovine pulmonary artery endothelial cells. J Biol Chem 273: 19679–19684

    Google Scholar 

  • Lafont F, Lecat S, Verkade P, Simons K (1998) Annexin XIIIb associates with lipid microdomains to function in apical delivery. J Cell Biol 142: 1413–1427

    Google Scholar 

  • Lambert O, Gerke V, Bader MF, Porte F, Brisson A (1997) Structural analysis of junctions formed between lipid membranes and several annexins by cryo-electron microscopy. J Mol Biol 272: 42–55

    Google Scholar 

  • Liemann S, Huber R (1997) Three-dimensional structure of annexins. Cell Mol Life Sci 53: 516–521

    Google Scholar 

  • —, Lewit-Bentley A (1995) Annexins: a novel family of calcium- and membrane-binding proteins in search of a function. Structure 3: 233–237

    Google Scholar 

  • Lin HC, Sudhof TC, Anderson RG (1992) Annexin VI is required for budding of clathrin-coated pits. Cell 70: 283–291

    Google Scholar 

  • Liu K, Li G (1998) Catalytic domain of the p120 Ras GAP binds to RAb5 and stimulates its GTPase activity. J Biol Chem 273: 10087–10090

    Google Scholar 

  • Liu Y, Casey L, Pike LJ (1998) Compartimentalization of phosphatidylinositol 4,5-biphosphate in low-density membrane domains in the absence of caveolin. Biochem Biophys Res Commun 245: 684–690

    Google Scholar 

  • Luecke H, Chang BT, Mailliard WS, Schlaepfer DD, Haigler HT (1995) Crystal structure of the annexin XII hexamer and implications for bilayer insertion. Nature 378: 512–515

    Google Scholar 

  • Matsuda R, Kaneko N, Horikawa Y (1997) Presence and comparison of Ca2+ transport activity of annexins I, II, V, and VI in large unilamellar vesicles. Biochem Biophys Res Commun 237: 499–503

    Google Scholar 

  • Mayor S, Sabharanjak S, Maxfield FR (1998) Cholesterol-dependent retention of GPI-anchored proteins in endosomes. EMBO J 17: 4626–4638

    Google Scholar 

  • Mayorga LS, Beron W, Sarrouf MN, Colombo MI, Creutz C, Stahl PD (1994) Calcium dependent fusion among endosomes. J Biol Chem 269: 30927–30934

    Google Scholar 

  • —, Colombo MI, Lennartz M, Brown EJ, Weiss R, Lennon PJ, Stahl PD (1993) Inhibition of endosome fusion by phospholipase A2 inhibitors points to a role for PLA2 in endocytosis. Proc Natl Acad Sci USA 90: 10255–10259

    Google Scholar 

  • Mochly-Rosen D, Khaner H, Lopez J, Smith RL (1991) Intracellular receptors for activated PKC: identification of a binding site for the enzyme. J Biol Chem 266: 14866–14868

    Google Scholar 

  • —, Miller KG, Scheller RH, Khamer H, Lopez J, Smith BL (1992) p65 fragments, homologous to the C2 region of PKC, bind to the intra-cellular receptors for PKC. Biochemistry 31: 8120–8124

    Google Scholar 

  • Morgan RO, Pilar FM (1997) Distinct annexin subfamilies in plants and protists diverged prior to animal annexins and from a common ancestor. J Mol Evol 44: 178–188

    Google Scholar 

  • Nakata T, Sobue K, Hirokawa N (1990) Conformational change and localization of calpactin I complex involved in exocytosis as revealed by quick-freeze, deep-etch electron microscopy and immunocytochemistry. J Cell Biol 110: 13–25

    Google Scholar 

  • Nalefski EA, Falke JJ (1996) The C2 domain calcium-binding motif: structural and functional diversity. Protein Sci 5: 2375–2390

    Google Scholar 

  • Niki I, Yokokura H, Sudo T, Kato M, Hidaka H (1996) Calcium signaling and intracellular calcium binding proteins. J Biochem 120: 685–698

    Google Scholar 

  • Ortega D, Pol A, Biermer M, Jackle S, Enrich C (1998) Annexin VI defines an apical endocytic compartment in rat liver hepatocytes. J Cell Sci 111: 261–269

    Google Scholar 

  • Parkin ET, Turner AJ, Hooper NM (1996) Isolation and characterization of two distinct low-density, Triton-insoluble, complexes from porcine lung membranes. Biochem J 319: 887–896

    Google Scholar 

  • Pike LJ, Miller JM (1998) Cholesterol depletion delocalizes phosphatidylinositol biphosphate and inhibits hormone-stimulated phosphatidylinositol turnover. J Biol Chem 273: 22298–22304

    Google Scholar 

  • Powell MA, Glenney JR Jr (1987) Regulation of calpactin I phospholipid binding by calpactin I light-chain binding and phosphorylation by pp60v-src. Biochem J 247: 321–328

    Google Scholar 

  • Raynal P, Hullin F, Ragab TJ, Fauvel J, Chap H (1993) Annexin 5 as a potential regulator of annexin l phosphorylation by protein kinase C: in vitro inhibition compared with quantitative data on annexin distribution in human endothelial cells. Biochem J 292: 759–765

    Google Scholar 

  • Regnouf F, Sagot I, Delouche B, Devilliers G, Cartaud J, Henry JP, Pradel LA (1995) “In vitro” phosphorylation of annexin II heterotetramer by PKC: comparative properties of the unphosphorylated and phosphorylated annexin II on the aggregation and fusion of chromaffin granule membranes. J Biol Chem 270: 27143–27150

    Google Scholar 

  • Roth D, Morgan A, Burgoyne RD (1993) Identification of a key domain in annexin and 14-3-3 proteins that stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells. FEBS Lett 320: 207–210

    Google Scholar 

  • Rothhut B (1997) Participation of annexins in protein phosphorylation. Cell Mol Life Sci 53: 522–526

    Google Scholar 

  • Sarafian T, Pradel LA, Henry JP, Aunis D, Bader MF (1991) The participation of annexin II (calpactin I) in calcium-evoked exocytosis requires protein kinase C. J Cell Biol 114: 1135–1147

    Google Scholar 

  • Sato K, Saito Y, Kawashima S (1995) Identification and characterization of membrane-bound calpains in clathrin-coated vesicles from bovine brain. Eur J Biochem 230: 25–31

    Google Scholar 

  • Schafer BW, Heizmann CW (1996) The S100 family of EF-hand calcium binding proteins: functions and pathology. Trends Biol Sci 21: 134–140

    Google Scholar 

  • Seemann J, Weber K, Gerke V (1997) Annexin I targets S100C to early endosomes. FEBS Lett 413: 185–190

    Google Scholar 

  • Siever DA, Erickson HP (1997) Extracellular annexin II. Int J Biochem Cell Biol 29: 1219–1223

    Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387: 569–572

    Google Scholar 

  • Smythe E, Smith PD, Jacob SM, Theobald J, Moss SE (1994) Endocytosis occurs independently of annexin VI in human A431 cells. J Cell Biol 124: 301–306

    Google Scholar 

  • Swairjo MA, Seaton BA (1994) Annexin structure and membrane interactions: a molecular perspective. Annu Rev Biophys Biomol Struct 23: 193–213

    Google Scholar 

  • Thorin B, Gache G, Dubois T, Gataroli R, Domingo N, Russo-Marie F, Lafont H (1995) Annexin VI is secreted in human bile. Biochem Biophys Res Commun 209: 1039–1045

    Google Scholar 

  • Turpin E, Russo-Marie F, Dubois T, de Paillerets C, Alfsen A, Bomsel M (1998) In adrenocortical tissue, annexins II and VI are attached to clathrin coated vesicles in a calcium-independent manner. Biochim Biophys Acta 1402: 115–130

    Google Scholar 

  • Watanabe M, Ando Y, Tokumitsu H, Hidaka H (1993) Binding site of annexin XI on the calcyclin molecule. Biochem Biophys Res Commun 196: 1376–1382

    Google Scholar 

  • Watanabe T, Inui M, Chen BY, Iga M, Sobue K (1994) Annexin VI-binding proteins in brain: interaction of annexin VI with a membrane skeletal protein, calspectin (brain spectrin or fodrin). J Biol Chem 269: 17656–17662

    Google Scholar 

  • Wice BM, Gordon JI (1992) A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin. J Cell Biol 116: 405–422

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Biology and Biophysics Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, Postfach 10 2209, D-69012, Heidelberg, Germany

    Sandra Lecat & Frank Lafont

  2. Max Planck Institute for Molecular Cell Biology and Genetics, Dresden

    Sandra Lecat & Frank Lafont

Authors
  1. Sandra Lecat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Lafont
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lecat, S., Lafont, F. Annexins and their interacting proteins in membrane traffic. Protoplasma 207, 133–140 (1999). https://doi.org/10.1007/BF01282992

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01282992

Keywords

Search

Navigation