Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Slp (Synaptotagmin-Like Protein)

  • Mitsunori FukudaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_560


Historical Background

Synaptotagmin-like proteins (Slps) were originally identified as synaptotagmin-related molecules containing two C2 calcium/phospholipid-binding motifs (named the C2A domain and the C2B domain) at their C terminus and no transmembrane domain at their N terminus (Fig. 1a), which suggested that they regulate certain intracellular membrane traffic events, the same as synaptotagmin I (Syt I) does in synaptic vesicle traffic (Fukuda and Mikoshiba 2001). The Slp family of proteins is now defined as a family of proteins, each of which contains an N-terminal conserved motif named the Slp homology domain (SHD) (Fig. 1a, magenta boxes) and C-terminal tandem C2 domains, although some members of the Slp family have several isoforms (e.g., Slp2-b, Slp3-b, and Slp4-b) that lack one of these domains because of alternative splicing (Fig. 1a, bars and arrows) (Fukuda et al. 2001). The Slp family is also recognized as the third group...
This is a preview of subscription content, log in to check access.


  1. Arimura N, Kimura T, Nakamuta S, Taya S, Funahashi Y, Hattori A, et al. Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell. 2009;16:675–86.  https://doi.org/10.1016/j.devcel.2009.03.005.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Brzezinska AA, Johnson JL, Munafo DB, Crozat K, Beutler B, Kiosses WB, et al. The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic. 2008;9:2151–64.  https://doi.org/10.1111/j.1600-0854.2008.00838.x.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Fukuda M. The C2A domain of synaptotagmin-like protein 3 (Slp3) is an atypical calcium-dependent phospholipid-binding machine: comparison with the C2A domain of synaptotagmin I. Biochem J. 2002;366:681–7.  https://doi.org/10.1042/BJ20020484.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Fukuda M. Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic. 2013;14:949–63.  https://doi.org/10.1111/tra.12083.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Fukuda M, Mikoshiba K. Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2 proteins. Biochem Biophys Res Commun. 2001;281:1226–33.  https://doi.org/10.1006/bbrc.2001.4512.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Fukuda M, Saegusa C, Mikoshiba K. Novel splicing isoforms of synaptotagmin-like proteins 2 and 3: identification of the Slp homology domain. Biochem Biophys Res Commun. 2001;283:513–9.  https://doi.org/10.1006/bbrc.2001.4803.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gálvez-Santisteban M, Rodriguez-Fraticelli AE, Bryant DM, Vergarajauregui S, Yasuda T, Bañón-Rodríguez I, et al. Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nat Cell Biol. 2012;14:838–49.  https://doi.org/10.1038/ncb2541.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T. Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol. 2005;171:99–109.  https://doi.org/10.1083/jcb.200505179.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Holt O, Kanno E, Bossi G, Booth S, Daniele T, Santoro A, et al. Slp1 and Slp2-a localize to the plasma membrane of CTL and contribute to secretion from the immunological synapse. Traffic. 2008;9:446–57.  https://doi.org/10.1111/j.1600-0854.2008.00714.x.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Kuroda TS, Fukuda M. Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Nat Cell Biol. 2004;6:1195–203.  https://doi.org/10.1038/ncb1197.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Kuroda TS, Fukuda M, Ariga H, Mikoshiba K. The Slp homology domain of synaptotagmin-like proteins 1-4 and Slac2 functions as a novel Rab27A binding domain. J Biol Chem. 2002a;277:9212–8.  https://doi.org/10.1074/jbc.M112414200.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Kuroda TS, Fukuda M, Ariga H, Mikoshiba K. Synaptotagmin-like protein 5: a novel Rab27A effector with C-terminal tandem C2 domains. Biochem Biophys Res Commun. 2002b;293:899–906.  https://doi.org/10.1016/S0006-291X(02)00320-0.CrossRefPubMedPubMedCentralGoogle Scholar
  13. McAdara Berkowitz JK, Catz SD, Johnson JL, Ruedi JM, Thon V, Babior BM. JFC1, a novel tandem C2 domain-containing protein associated with the leukocyte NADPH oxidase. J Biol Chem. 2001;276:18855–62.  https://doi.org/10.1074/jbc.M011167200.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Neumüller O, Hoffmeister M, Babica J, Prelle C, Gegenbauer K, Smolenski AP. Synaptotagmin-like protein 1 interacts with the GTPase-activating protein Rap1GAP2 and regulates dense granule secretion in platelets. Blood. 2009;114:1396–404.  https://doi.org/10.1182/blood-2008-05-155234.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19–30.  https://doi.org/10.1038/ncb2000.CrossRefPubMedGoogle Scholar
  16. Saegusa C, Tanaka T, Tani S, Itohara S, Mikoshiba K, Fukuda M. Decreased basal mucus secretion by Slp2-a-deficient gastric surface mucous cells. Genes Cells. 2006;11:623–31.  https://doi.org/10.1111/j.1365-2443.2006.00964.x.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Tomas A, Meda P, Regazzi R, Pessin JE, Halban PA. Munc 18-1 and granuphilin collaborate during insulin granule exocytosis. Traffic. 2008;9:813–32.  https://doi.org/10.1111/j.1600-0854.2008.00709.x.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Tsuboi T, Fukuda M. The Slp4-a linker domain controls exocytosis through interaction with Munc18-1·syntaxin-1a complex. Mol Biol Cell. 2006;17:2101–12.  https://doi.org/10.1091/mbc.E05-11-1047.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Wang J, Takeuchi T, Yokota H, Izumi T. Novel rabphilin-3-like protein associates with insulin-containing granules in pancreatic beta cells. J Biol Chem. 1999;274:28542–8.  https://doi.org/10.1074/jbc.274.40.28542.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Yasuda T, Fukuda M. Slp2-a controls renal epithelial cell size through regulation of Rap-ezrin signaling independently of Rab27. J Cell Sci. 2014;127:557–70.  https://doi.org/10.1242/jcs.134056.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and NeurosciencesGraduate School of Life Sciences, Tohoku UniversitySendaiJapan