Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Synapsins (SYN)

  • Sang-Ho Song
  • George J. Augustine
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101889

Synonyms

Historical Background

Synapsins were the first proteins identified in presynaptic terminals: Paul Greengard and colleagues identified protein I (now synapsin I, Kuo and Greengard 1969) as a major neuronal substrate for the cyclic AMP-dependent protein kinase (PKA) in rat brain (Johnson et al. 1972; Ueda et al. 1973). Protein I was also the first identified substrate of the Ca 2+/calmodulin-dependent protein kinase (De Camilli et al. 1990), indicating that synapsins serve as a central hub of numerous protein kinase signaling pathways (see below). Early on, it was appreciated that there are multiple synapsins; two isoforms, protein Ia (86 kDa) and Ib (80 kDa), could be distinguished by their molecular weights (Forn and Greengard 1978). We now know that there are even more synapsin isoforms (see Fig. 1). Protein I was found to be enriched in presynaptic terminals and bound to synaptic vesicles within these terminals, causing it to be renamed synapsin I...
This is a preview of subscription content, log in to check access.

References

  1. Cheetham JJ, Hilfiker S, Benfenati F, Weber T, Greengard P, Czernik AJ. Identification of synapsin I peptides that insert into lipid membranes. Biochem J. 2001;354:57–66.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Chi P, Greengard P, Ryan TA. Synaptic vesicle mobilization is regulated by distinct synapsin I phosphorylation pathways at different frequencies. Neuron. 2003;38:69–78.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Chin LS, LI L, Ferreira A, Kosik KS, Greengard P. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci U S A. 1995;92:9230–4.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Czernik AJ, Pang DT, Greengard P. Amino acid sequences surrounding the cAMP-dependent and calcium/calmodulin-dependent phosphorylation sites in rat and bovine synapsin I. Proc Natl Acad Sci USA. 1987;84:7518–22.PubMedPubMedCentralCrossRefGoogle Scholar
  5. De Camilli P, Cameron R, Greengard P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol. 1983;96:1337–54.PubMedPubMedCentralCrossRefGoogle Scholar
  6. De Camilli P, Benfenati F, Valtorta F, Greengard P. The synapsins. Annu Rev Cell Biol. 1990;6:433–60.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Feng J, Chi P, Blanpied TA, Xu Y, Magarinos AM, Ferreira A, Takahashi RH, Kao HT, Mcewen BS, Ryan TA, Augustine GJ, Greengard P. Regulation of neurotransmitter release by synapsin III. J Neurosci. 2002;22:4372–80.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Ferreira A, Li L, Chin LS, Greengard P, Kosik KS. Postsynaptic element contributes to the delay in synaptogenesis in synapsin I-deficient neurons. Mol Cell Neurosci. 1996;8:286–99.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ferreira A, Chin LS, Li L, Lanier LM, Kosik KS, Greengard P. Distinct roles of synapsin I and synapsin II during neuronal development. Mol Med. 1998;4:22–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Forn J, Greengard P. Depolarizing agents and cyclic nucleotides regulate the phosphorylation of specific neuronal proteins in rat cerebral cortex slices. Proc Natl Acad Sci USA. 1978;75:5195–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Gitler D, Xu Y, Kao HT, Lin D, Lim S, Feng J, Greengard P, Augustine GJ. Molecular determinants of synapsin targeting to presynaptic terminals. J Neurosci. 2004a;24:3711–20.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Gitler D, Takagishi Y, Feng J, Ren Y, Rodriguiz RM, Wetsel WC, Greengard P, Augustine GJ. Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J Neurosci. 2004b;24:11368–80.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Gitler D, Cheng Q, Greengard P, Augustine GJ. Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles. J Neurosci. 2008;28:10835–43.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Hilfiker S, Schweizer FE, Kao HT, Czernik AJ, Greengard P, Augustine GJ. Two sites of action for synapsin domain E in regulating neurotransmitter release. Nat Neurosci. 1998;1:29–35.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Hilfiker S, Benfenati F, Doussau F, Nairn AC, Czernik AJ, Augustine GJ, Greengard P. Structural domains involved in the regulation of transmitter release by synapsins. J Neurosci. 2005;25:2658–69.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Hosaka M, Sudhof TC. Homo- and heterodimerization of synapsins. J Biol Chem. 1999;274:16747–53.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Johnson EM, Ueda T, Maeno H, Greengard P. Adenosine 3′, 5-monophosphate-dependent phosphorylation of a specific protein in synaptic membrane fractions from rat cerebrum. J Biol Chem. 1972;247:5650–2.PubMedPubMedCentralGoogle Scholar
  18. Kao HT, Porton B, Czernik AJ, Feng J, Yiu G, Haring M, Benfenati F, Greengard P. A third member of the synapsin gene family. Proc Natl Acad Sci USA. 1998;95:4667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Kile BM, Guillot TS, Venton BJ, Wetsel WC, Augustine GJ, Wightman RM. Synapsins differentially control dopamine and serotonin release. J Neurosci. 2010;30:9762–70.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Kuo JF, Greengard P. Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3′ ,5′ -monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci USA. 1969;64:1349–55.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Li L, Chin LS, Greengard P, Copeland NG, Gilbert DJ, Jenkins NA. Localization of the synapsin II (SYN2) gene to human chromosome 3 and mouse chromosome 6. Genomics. 1995;28:365–6.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Pieribone VA, Shupliakov O, Brodin L, Hilfiker-Rothenfluh S, Czernik AJ, Greengard P. Distinct pools of synaptic vesicles in neurotransmitter release. Nature. 1995;375:493–7.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Porton B, Ferreira A, Delisi LE, Kao HT. A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia. Biol Psychiatry. 2004;55:118–25.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Rosahl TW, Spillane D, Missler M, Herz J, Selig DK, Wolff JR, Hammer RE, Malenka RC, Sudhof TC. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature. 1995;375:488–93.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Song SH, Augustine GJ. Synapsin isoforms regulating GABA release from hippocampal interneurons. J Neurosci. 2016;36:6742–57.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Sudhof TC, Czernik AJ, Kao HT, Takei K, Johnston PA, Horiuchi A, Kanazir SD, Wagner MA, Perin MS, De Camilli P, et al. Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins. Science. 1989;245:1474–80.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Ueda T, Maeno H, Greengard P. Regulation of endogenous phosphorylation of specific proteins in synaptic membrane fractions from rat brain by adenosine 3′:5′ -monophosphate. J Biol Chem. 1973;248:8295–305.PubMedPubMedCentralGoogle Scholar
  28. Venton BJ, Seipel AT, Phillips PE, Wetsel WC, Gitler D, Greengard P, Augustine GJ, Wightman RM. Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool. J Neurosci. 2006;26:3206–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Villanueva M, Thornley K, Augustine GJ, Wightman RM. Synapsin II negatively regulates catecholamine release. Brain Cell Biol. 2006;35:125–36.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Yang-Feng TL, Degennaro LJ, Francke U. Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci U S A. 1986;83:8679–83.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
  2. 2.Institute of Molecular and Cell BiologyA*STARSingaporeSingapore