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S100A10/p11: family, friends and functions

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Abstract

S100A10, also known as p11 or annexin 2 light chain, is a member of the S100 family of small, dimeric EF hand-type Ca2+-binding proteins that generally modulate cellular target proteins in response to intracellular Ca2+ signals. In contrast to all other S100 proteins, S100A10 is Ca2+ insensitive because of amino acid replacements in its Ca2+-binding loops that lock the protein in a permanently active state. Within cells, the majority of S100A10 resides in a tight heterotetrameric complex with the peripheral membrane-binding protein annexin A2 that directs the complex to specific target membranes, in particular the plasma membrane and the membrane of early endosomes. Several other Ca2+-independent interaction partners of S100A10 have been described in the recent past. Many of these interactions, which have been shown to be of functional significance for the respective partner, involve plasma membrane-resident proteins. In most of these cases, S100A10, probably residing in a complex with annexin A2, appears to regulate the intracellular trafficking of the respective target protein and thus its functional expression at the cell surface. In this paper, we review the current information on S100A10 protein interactions placing a particular emphasis on data that contribute to an understanding of the mechanistic basis of the S100A10 action. Based on these data, we propose that S100A10 functions as a linker tethering certain transmembrane proteins to annexin A2 thereby assisting their traffic to the plasma membrane and/or their firm anchorage at certain membrane sites.

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References

  1. Marenholz I, Lovering RC, Heizmann CW (2006) An update of the S100 nomenclature. Biochim Biophys Acta 1763:1282–1283

    Article  PubMed  CAS  Google Scholar 

  2. Moore B (1965) A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 19:739–744

    Article  PubMed  CAS  Google Scholar 

  3. Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322:1111–1122

    Article  PubMed  CAS  Google Scholar 

  4. Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33:637–668

    Article  PubMed  CAS  Google Scholar 

  5. Bhattacharya S, Bunick CG, Chazin WJ (2004) Target selectivity in EF-hand calcium binding proteins. Biochim Biophys Acta 1742:69–79

    Article  PubMed  CAS  Google Scholar 

  6. Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396:201–214

    Article  PubMed  CAS  Google Scholar 

  7. Gerke V, Weber K (1984) Identity of p36K phosphorylated upon Rous sarcoma virus transformation with a protein purified from brush borders; calcium-dependent binding to non-erythroid spectrin and F-actin. EMBO J 3:227–233

    PubMed  CAS  Google Scholar 

  8. Gerke V, Weber K (1985) The regulatory chain in the p36-kd substrate complex of viral tyrosine-specific protein kinases is related in sequence to the S-100 protein of glial cells. EMBO J 4:2917–2920

    PubMed  CAS  Google Scholar 

  9. Glenney JR Jr, Tack BF (1985) Amino-terminal sequence of p36 and associated p10: identification of the site of tyrosine phosphorylation and homology with S-100. Proc Natl Acad Sci USA 82:7884–7888

    Article  PubMed  CAS  Google Scholar 

  10. Saris CJ, Kristensen T, D’Eustachio P, Hicks LJ, Noonan DJ, Hunter T, Tack BF (1987) cDNA sequence and tissue distribution of the mRNA for bovine and murine p11, the S100-related light chain of the protein-tyrosine kinase substrate p36 (calpactin I). J Biol Chem 262:10663–10671

    PubMed  CAS  Google Scholar 

  11. Zokas L, Glenney JR Jr (1987) The calpactin light chain is tightly linked to the cytoskeletal form of calpactin I: studies using monoclonal antibodies to calpactin subunits. J Cell Biol 105:2111–2121

    Article  PubMed  CAS  Google Scholar 

  12. Harder T, Kube E, Gerke V (1992) Cloning and characterization of the human gene encoding p11: structural similarity to other members of the S-100 gene family. Gene 113:269–274

    Article  PubMed  CAS  Google Scholar 

  13. Huang XL, Pawliczak R, Yao XL, Cowan MJ, Gladwin MT, Walter MJ, Holtzman MJ, Madara P, Logun C, Shelhamer JH (2003) Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter. J Biol Chem 278:9298–9308

    Article  PubMed  CAS  Google Scholar 

  14. Glenney J (1986) Phospholipid-dependent Ca2+ binding by the 36-kDa tyrosine kinase substrate (calpactin) and its 33-kDa core. J Biol Chem 261:7247–7252

    PubMed  CAS  Google Scholar 

  15. Rety S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A (1999) The crystal structure of a complex of p11 with the annexin II N-terminal peptide. Nat Struct Biol 6:89–95

    Article  PubMed  CAS  Google Scholar 

  16. Kube E, Becker T, Weber K, Gerke V (1992) Protein-protein interaction studied by site-directed mutagenesis. Characterization of the annexin II-binding site on p11, a member of the S100 protein family. J Biol Chem 267:14175–14182

    PubMed  CAS  Google Scholar 

  17. Gerke V, Creutz CE, Moss SE (2005) Annexins: linking Ca2+signalling to membrane dynamics. Nat Rev Mol Cell Biol 6:449–461

    Article  PubMed  CAS  Google Scholar 

  18. Lewit-Bentley A, Rety S, Sopkova-de Oliveira Santos J, Gerke V (2000) S100–annexin complexes: some insights from structural studies. Cell Biol Int 24:799–802

    Article  PubMed  CAS  Google Scholar 

  19. Johnsson N, Gerke V, Weber K (1990) P36, member of the Ca2+/lipid binding proteins (annexins, calpactins, lipocortins) and its complex with P11; molecular aspects. Prog Clin Biol Res 349:123–133

    PubMed  CAS  Google Scholar 

  20. Becker T, Weber K, Johnsson N (1990) Protein-protein recognition via short amphiphilic helices; a mutational analysis of the binding site of annexin II for p11. EMBO J 9:4207–4213

    PubMed  CAS  Google Scholar 

  21. 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

    Article  PubMed  CAS  Google Scholar 

  22. Menke M, Ross M, Gerke V, Steinem C (2004) The molecular arrangement of membrane-bound annexin A2–S100A10 tetramer as revealed by scanning force microscopy. Chembiochem 5:1003–1006

    Article  PubMed  CAS  Google Scholar 

  23. Rescher U, Gerke V (2004) Annexins—unique membrane binding proteins with diverse functions. J Cell Sci 117:2631–2639

    Article  PubMed  CAS  Google Scholar 

  24. Hayes MJ, Merrifield CJ, Shao D, Ayala-Sanmartin J, Schorey CD, Levine TP, Proust J, Curran J, Bailly M, Moss SE (2004) Annexin 2 binding to phosphatidylinositol 4,5-bisphosphate on endocytic vesicles is regulated by the stress response pathway. J Biol Chem 279:14157–14164

    Article  PubMed  CAS  Google Scholar 

  25. Rescher U, Ruhe D, Ludwig C, Zobiack N, Gerke V (2004) Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assembly sites at cellular membranes. J Cell Sci 117:3473–3480

    Article  PubMed  CAS  Google Scholar 

  26. Hayes MJ, Rescher U, Gerke V, Moss SE (2004) Annexin-actin interactions. Traffic 5:571–576

    Article  PubMed  CAS  Google Scholar 

  27. Hayes MJ, Shao D, Bailly M, Moss SE (2006) Regulation of actin dynamics by annexin 2. EMBO J 25:1816–1826

    Article  PubMed  CAS  Google Scholar 

  28. Martin-Belmonte F, Gassama A, Datta A, Yu W, Rescher U, Gerke V, Mostov K (2007) PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128:383–397

    Article  PubMed  CAS  Google Scholar 

  29. Puisieux A, Ji J, Ozturk M (1996) Annexin II up-regulates cellular levels of p11 protein by a post-translational mechanisms. Biochem J 313(Pt 1):51–55

    PubMed  CAS  Google Scholar 

  30. Okuse K, Malik-Hall M, Baker MD, Poon WY, Kong H, Chao MV, Wood JN (2002) Annexin II light chain regulates sensory neuron-specific sodium channel expression. Nature 417:653–656

    Article  PubMed  CAS  Google Scholar 

  31. Poon WY, Malik-Hall M, Wood JN, Okuse K (2004) Identification of binding domains in the sodium channel Na(V)1.8 intracellular N-terminal region and annexin II light chain p11. FEBS Lett 558:114–118

    Article  PubMed  CAS  Google Scholar 

  32. Girard C, Tinel N, Terrenoire C, Romey G, Lazdunski M, Borsotto M (2002) p11, an annexin II subunit, an auxiliary protein associated with the background K + channel, TASK-1. EMBO J 21:4439–4448

    Article  PubMed  CAS  Google Scholar 

  33. Renigunta V, Yuan H, Zuzarte M, Rinne S, Koch A, Wischmeyer E, Schlichthorl G, Gao Y, Karschin A, Jacob R, Schwappach B, Daut J, Preisig-Muller R (2006) The retention factor p11 confers an endoplasmic reticulum-localization signal to the potassium channel TASK-1. Traffic 7:168–181

    Article  PubMed  CAS  Google Scholar 

  34. van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, Gerke V, Staub O, Nilius B, Bindels RJ (2003) Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex. EMBO J 22:1478–1487

    Article  PubMed  Google Scholar 

  35. Donier E, Rugiero F, Okuse K, Wood JN (2005) Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a. J Biol Chem 280:38666–38672

    Article  PubMed  CAS  Google Scholar 

  36. Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG, Greengard P (2006) Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 311:77–80

    Article  PubMed  CAS  Google Scholar 

  37. Benaud C, Gentil BJ, Assard N, Court M, Garin J, Delphin C, Baudier J (2004) AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture. J Cell Biol 164:133–144

    Article  PubMed  CAS  Google Scholar 

  38. De Seranno S, Benaud C, Assard N, Khediri S, Gerke V, Baudier J, Delphin C (2006) Identification of an AHNAK binding motif specific for the Annexin2/S100A10 tetramer. J Biol Chem 281:35030–35038

    Article  PubMed  Google Scholar 

  39. Beaton AR, Rodriguez J, Reddy YK, Roy P (2002) The membrane trafficking protein calpactin forms a complex with bluetongue virus protein NS3 and mediates virus release. Proc Natl Acad Sci USA 99:13154–13159

    Article  PubMed  CAS  Google Scholar 

  40. Kim J, Hajjar KA (2002) Annexin II: a plasminogen-plasminogen activator co-receptor. Front Biosci 7:d341–d348

    Article  PubMed  CAS  Google Scholar 

  41. Kwon M, MacLeod TJ, Zhang Y, Waisman DM (2005) S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors. Front Biosci 10:300–325

    Article  PubMed  CAS  Google Scholar 

  42. Deora AB, Kreitzer G, Jacovina AT, Hajjar KA (2004) An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface. J Biol Chem 279:43411–43418

    Article  PubMed  CAS  Google Scholar 

  43. Cesarman-Maus G, Hajjar KA (2005) Molecular mechanisms of fibrinolysis. Br J Haematol 129:307–321

    Article  PubMed  CAS  Google Scholar 

  44. Waisman DM (2005) Annexin A2 may not play a role as a plasminogen receptor. Br J Haematol 131:553–554 author reply 554–556

    Article  PubMed  CAS  Google Scholar 

  45. Foulkes T, Nassar MA, Lane T, Matthews EA, Baker MD, Gerke V, Okuse K, Dickenson AH, Wood JN (2006) Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior. J Neurosci 26:10499–10507

    Article  PubMed  CAS  Google Scholar 

  46. Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa LC, Dickenson AH, Wood JN (1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2:541–548

    Article  PubMed  CAS  Google Scholar 

  47. Verma R, Cutler DJ, Holmans P, Knowles JA, Crowe RR, Scheftner WA, Weissman MM, Depaulo JR Jr, Levinson DF, Potash JB (2007) Investigating the role of p11 (S100A10) sequence variation in susceptibility to major depression. Am J Med Genet B Neuropsychiatr Genet (in press)

  48. Rajan S, Preisig-Muller R, Wischmeyer E, Nehring R, Hanley PJ, Renigunta V, Musset B, Schlichthorl G, Derst C, Karschin A, Daut J (2002) Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3. J Physiol 545:13–26

    Article  PubMed  CAS  Google Scholar 

  49. O’Kelly I, Butler MH, Zilberberg N, Goldstein SA (2002) Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell 111:577–588

    Article  PubMed  CAS  Google Scholar 

  50. Martens JR, O’Connell K, Tamkun M (2004) Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts. Trends Pharmacol Sci 25:16–21

    Article  PubMed  CAS  Google Scholar 

  51. Eisensamer B, Uhr M, Meyr S, Gimpl G, Deiml T, Rammes G, Lambert JJ, Zieglgansberger W, Holsboer F, Rupprecht R (2005) Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains. J Neurosci 25:10198–10206

    Article  PubMed  CAS  Google Scholar 

  52. Kalipatnapu S, Chattopadhyay A (2005) Membrane organization of the human serotonin(1A) receptor monitored by detergent insolubility using GFP fluorescence. Mol Membr Biol 22:539–547

    Article  PubMed  CAS  Google Scholar 

  53. Ambudkar IS, Bandyopadhyay BC, Liu X, Lockwich TP, Paria B, Ong HL (2006) Functional organization of TRPC-Ca2+ channels and regulation of calcium microdomains. Cell Calcium 40:495–504

    Article  PubMed  CAS  Google Scholar 

  54. Mayran N, Parton RG, Gruenberg J (2003) Annexin II regulates multivesicular endosome biogenesis in the degradation pathway of animal cells. EMBO J 22:3242–3253

    Article  PubMed  CAS  Google Scholar 

  55. Zobiack N, Rescher U, Ludwig C, Zeuschner D, Gerke V (2003) The annexin 2/S100A10 complex controls the distribution of transferrin receptor-containing recycling endosomes. Mol Biol Cell 14:4896–4908

    Article  PubMed  CAS  Google Scholar 

  56. Johnsson N, Nguyen Van P, Soling HD, Weber K (1986) Functionally distinct serine phosphorylation sites of p36, the cellular substrate of retroviral protein kinase; differential inhibition of reassociation with p11. EMBO J 5:3455–3460

    PubMed  CAS  Google Scholar 

  57. Jost M, Gerke V (1996) Mapping of a regulatory important site for protein kinase C phosphorylation in the N-terminal domain of annexin II. Biochim Biophys Acta 1313:283–289

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank J. Daut (University of Marburg) for comments on the manuscript and the Deutsche Forschungsgemeinschaft (DFG), the Interdisciplinary Centre for Clinical Research (IZKF) and the Innovative Medical Research (IMF) of the Münster Medical School for support.

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  1. Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, 48149, Muenster, Germany

    Ursula Rescher & Volker Gerke

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  1. Ursula Rescher
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  2. Volker Gerke
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Correspondence to Ursula Rescher.

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Rescher, U., Gerke, V. S100A10/p11: family, friends and functions. Pflugers Arch - Eur J Physiol 455, 575–582 (2008). https://doi.org/10.1007/s00424-007-0313-4

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