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Synapsin

Synapsin, N-terminal domain
Structure of the c domain of synapsin IA from bovine brain.[1]
Identifiers
SymbolSynapsin
PfamPF02078
InterProIPR001359
PROSITEPDOC00345
SCOP21auv / SCOPe / SUPFAM
OPM superfamily123
OPM protein1auv
Membranome349
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Synapsin, ATP binding domain
Identifiers
SymbolSynapsin_C
PfamPF02750
InterProIPR001359
PROSITEPDOC00345
SCOP21auv / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1auv​ , 1aux​ , 1i7l​ , 1i7n​ , 1pk8​ , 1px2​ , 2p0a​

The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.[2] Synapsins are present in invertebrates and vertebrates and are strongly conserved across all species.[2] They are expressed in highest concentration in the nervous system, although they also express in other body systems such as the reproductive organs, including both eggs and spermatozoa. Synapsin function also increases as the organism matures, reaching its peak at sexual maturity.[3]

Current studies suggest the following hypothesis for the role of synapsin: synapsins bind synaptic vesicles to components of the cytoskeleton which prevents them from migrating to the presynaptic membrane and releasing neurotransmitter. During an action potential, synapsins are phosphorylated by PKA (cAMP dependent protein kinase), releasing the synaptic vesicles and allowing them to move to the membrane and release their neurotransmitter.

Gene knockout studies in mice (where the mouse is unable to produce synapsin) have had some surprising results. Consistently, knockout studies have shown that mice lacking one or more synapsins have defects in synaptic transmission induced by high‐frequency stimulation, suggesting that the synapsins may be one of the factors boosting release probability in synapses at high firing rates, such as by aiding the recruitment of vesicles from the reserve pool.[2] Furthermore, mice lacking all three synapsins are prone to seizures, and experience learning defects.[4] These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role. Lastly, observed effects seemed to vary between inhibitory and excitatory synapses, suggesting synapsins may play a slightly different role in each type.[2]

Family members

Humans and most other vertebrates possess three genes encoding three different synapsin proteins.[5] Each gene in turn is alternatively spliced to produce at least two different protein isoforms for a total of six isoforms:[6]

Gene Protein Isoforms
SYN1 Synapsin I Ia, Ib
SYN2 Synapsin II IIa, IIb
SYN3 Synapsin III IIIa, IIIb

Different neuron terminals will express varying amounts of each of these synapsin proteins and collectively these synapsins will comprise 1% of the total expressed protein at any one time.[7] Synapsin Ia has been implicated in bipolar disorder and schizophrenia.[8]

References

  1. ^ Esser L, Wang CR, Hosaka M, Smagula CS, Südhof TC, Deisenhofer J (February 1998). "Synapsin I is structurally similar to ATP-utilizing enzymes". EMBO J. 17 (4): 977–84. doi:10.1093/emboj/17.4.977. PMC 1170447. PMID 9463376.
  2. ^ a b c d Evergren E, Benfenati F, Shupliakov O (September 2007). "The synapsin cycle: a view from the synaptic endocytic zone". J. Neurosci. Res. 85 (12): 2648–56. doi:10.1002/jnr.21176. PMID 17455288. S2CID 7496079.
  3. ^ Maiole, Federica; Tedeschi, Giulia; Candiani, Simona; Maragliano, Luca; Benfenati, Fabio; Zullo, Letizia (2019-10-28). "Synapsins are expressed at neuronal and non-neuronal locations in Octopus vulgaris". Scientific Reports. 9 (1): 15430. Bibcode:2019NatSR...915430M. doi:10.1038/s41598-019-51899-y. ISSN 2045-2322. PMC 6817820. PMID 31659209.
  4. ^ Rosahl TW, Geppert M, Spillane D, Herz J, Hammer RE, Malenka RC, Sudhof TC (1993). "Short-term synaptic plasticity is altered in mice lacking synapsin I". Cell. 75 (4): 661–670. doi:10.1016/0092-8674(93)90487-B. PMID 7902212.
  5. ^ Kao HT, Porton B, Hilfiker S, Stefani G, Pieribone VA, DeSalle R, Greengard P (December 1999). "Molecular evolution of the synapsin gene family". J. Exp. Zool. 285 (4): 360–77. Bibcode:1999JEZ...285..360K. doi:10.1002/(SICI)1097-010X(19991215)285:4<360::AID-JEZ4>3.0.CO;2-3. PMID 10578110.
  6. ^ Gitler D, Xu Y, Kao HT, Lin D, Lim S, Feng J, Greengard P, Augustine GJ (April 2004). "Molecular determinants of synapsin targeting to presynaptic terminals". J. Neurosci. 24 (14): 3711–20. doi:10.1523/JNEUROSCI.5225-03.2004. PMC 6729754. PMID 15071120.
  7. ^ Ferreira A, Rapoport M (April 2002). "The synapsins: beyond the regulation of neurotransmitter release". Cell. Mol. Life Sci. 59 (4): 589–95. doi:10.1007/s00018-002-8451-5. PMC 11337460. PMID 12022468. S2CID 32337670.
  8. ^ Vawter, MP; et al. (April 2002). "Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia". Mol. Psychiatry. 7 (6): 571–8. doi:10.1038/sj.mp.4001158. PMID 12140780.
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