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Regulation of SNAREs: Complexin

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Abstract

Complexin (also called as synaphin), a small cytoplasmic protein, binds to SNAP receptor (SNARE) complex (membrane fusion machinery) and regulates neurotransmitter release at the post-priming stage. Several lines of evidence have demonstrated that complexin has at least two independent roles: clamping of the trans-SNARE complex and activation of Ca2+-triggered synchronous release of neurotransmitter. Both functions require its central SNARE binding domain. Recent studies suggest that complexin contains several functional domains that either stimulate or inhibit neurotransmitter release. Thus, the function of complexin is likely more complex than expected from its small size.

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References

  • Abderrahmani A, Niederhauser G, Plaisance V et al (2004) Complexin I regulates glucose-induced secretion in pancreatic beta-cells. J Cell Sci 117:2239–2247

    Article  CAS  PubMed  Google Scholar 

  • Augustine GJ, Charlton MP, Smith SJ (1985) Calcium entry and transmitter release at voltage-clamped nerve terminals of squid. J Physiol 367:163–181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bracher A, Kadlec J, Betz H, Weissenhorn W (2002) X-ray structure of a neuronal complexin-SNARE complex from squid. J Biol Chem 277:26517–26523

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Tomchick DR, Kovrigin E et al (2002) Three-dimensional structure of the complexin/SNARE complex. Neuron 33:397–409

    Article  CAS  PubMed  Google Scholar 

  • Dhara M, Yarzagaray A, Schwarz Y et al (2014) Complexin synchronizes primed vesicle exocytosis and regulates fusion pore dynamics. J Cell Biol 204:1123–1140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Geppert M, Goda Y, Hammer RE et al (1994) Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 79:717–727

    Article  CAS  PubMed  Google Scholar 

  • Giraudo CG, Eng WS, Melia TJ, Rothman JE (2006) A clamping mechanism involved in SNARE-dependent exocytosis. Science 313:676–680

    Article  CAS  PubMed  Google Scholar 

  • Giraudo CG, Garcia-Diaz A, Eng WS (2009) Alternative zippering as an on-off switch for SNARE-mediated fusion. Science 323:512–516

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huntwork S, Littleton JT (2007) A complexin fusion clamp regulates spontaneous neurotransmitter release and synaptic growth. Nat Neurosci 10:1235–1237

    Article  CAS  PubMed  Google Scholar 

  • Ishizuka T, Saisu H, Odani S, Abe T (1995) Synaphin: a protein associated with the docking/fusion complex in presynaptic terminals. Biochem Biophys Res Commun 213:1107–1114

    Article  CAS  PubMed  Google Scholar 

  • Ishizuka T, Saisu H, Odani S et al (1999) Distinct regional distribution in the brain of messenger RNAs for the two isoforms of synaphin associated with the docking/fusion complex. Neuroscience 88:295–306

    Article  CAS  PubMed  Google Scholar 

  • Itakura M, Misawa H, Sekiguchi M et al (1999) Transfection analysis of functional roles of complexin I and II in the exocytosis of two different types of secretory vesicles. Biochem Biophys Res Commun 265:691–696

    Article  CAS  PubMed  Google Scholar 

  • Kasai H, Takahashi N, Tokumaru H (2012) Distinct initial SNARE configurations underlying the diversity of exocytosis. Physiol Rev 92:1915–1964

    Article  CAS  PubMed  Google Scholar 

  • Lai AL, Huang H, Herrick DZ et al (2011) Synaptotagmin 1 and SNAREs form a complex that is structurally heterogeneous. J Mol Biol 405:696–706

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li Y, Augustine GJ, Weninger K (2007) Kinetics of complexin binding to the SNARE complex: correcting single molecule FRET measurements for hidden events. Biophys J 93:2178–2187

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Llinas R, Steinberg IZ, Walton K (1981) Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys J 33:323–351

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Malsam J, Seiler F, Schollmeier Y et al (2009) The carboxy-terminal domain of complexin I stimulates liposome fusion. Proc Natl Acad Sci U S A 106:2001–2006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maximov A, Tang J, Yang X et al (2009) Complexin controls the force transfer from SNARE complexes to membranes in fusion. Science 323:516–521

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McMahon HT, Missler M, Li C, Sudhof TC (1995) Complexins: cytosolic proteins that regulate SNAP receptor function. Cell 83:111–119

    Article  CAS  PubMed  Google Scholar 

  • Pabst S, Margittai M, Vainius D et al (2002) Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis. J Biol Chem 277:7838–7848

    Article  CAS  PubMed  Google Scholar 

  • Reim K, Mansour M, Varoqueaux F et al (2001) Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell 104:71–81

    Article  CAS  PubMed  Google Scholar 

  • Reim K, Wegmeyer H, Brandstatter JH et al (2005) Structurally and functionally unique complexins at retinal ribbon synapses. J Cell Biol 169:669–680

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schaub JR, Lu X, Doneske B et al (2006) Hemifusion arrest by complexion is relieved by Ca2+ -Synaptotagmin I. Nat Struct Mol Biol 13:748–750

    Article  CAS  PubMed  Google Scholar 

  • Takahashi S, Yamamoto H, Matsuda Z (1995) Identification of two highly homologous presynaptic proteins distinctly localized at the dendritic and somatic synapses. FEBS Lett 368:455–460

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Maximov A, Shin OH et al (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126:1175–1187

    Article  CAS  PubMed  Google Scholar 

  • Tokumaru H, Umayahara K, Pellegrini LL et al (2001) SNARE complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis. Cell 104:421–432

    Article  CAS  PubMed  Google Scholar 

  • Tokumaru H, Shimizu-Okabe C, Abe T (2008) Direct interaction of SNARE complex binding protein synaphin/complexin with calcium sensor synaptotagmin 1. Brain Cell Biol 36:173–189

    Article  CAS  PubMed  Google Scholar 

  • Xue M, Reim K, Chen X et al (2007) Distinct domains of complexin I differentially regulate neurotransmitter release. Nat Struct Mol Biol 14:949–958

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Cao P, Südhof TC (2013) Deconstructing complexin function in activating and clamping Ca2+-triggered exocytosis by comparing knockout and knockdown phenotypes. Proc Natl Acad Sci U S A 110:20777–20782

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou A, Brewer KD, Rizo J (2013) Analysis of SNARE complex/synaptotagmin-1 interactions by one-dimensional NMR spectroscopy. Biochemistry 52:3446–3456

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Hiroshi Tokumaru .

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Tokumaru, H. (2015). Regulation of SNAREs: Complexin. In: Mochida, S. (eds) Presynaptic Terminals. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55166-9_6

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