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Synapsin

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This is an old revision of this page, as edited by 131.111.109.40 (talk) at 15:46, 15 November 2016 (As mentioned in talk page, the reference (Kihara PMID 18248909) found the exact opposite. The authors found that synapsin I expression was NOT reduced by knocking out synaptic activity, but some other proteins were). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

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 superfamily131
OPM protein1auv
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 somewhat homologous across evaluated vertebrates.

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. Mice lacking all three synapsins are prone to seizures, and experience learning defects.[3] These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role.

Family members

Humans and most other vertebrates possess three genes encoding three different synapsin proteins.[4] Each gene in turn is alternatively spliced to produce at least two different protein isoforms for a total of six isoforms:[5]

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.[6] Synapsin Ia has been implicated in bipolar disorder and schizophrenia.[7]

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. ^ 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.
  3. ^ 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.
  4. ^ 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. doi:10.1002/(SICI)1097-010X(19991215)285:4<360::AID-JEZ4>3.0.CO;2-3. PMID 10578110.
  5. ^ 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. PMID 15071120.
  6. ^ 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. PMID 12022468.
  7. ^ 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.