Synaptotagmin: Difference between revisions
Michal Harel (talk | contribs) New page: <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> == Function == '''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein a... |
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<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
== Function == | == Function == | ||
'''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions<ref>PMID:19412166</ref>. The C2A domain of SYT binds phospholipids in Ca+2-dpendent manner<ref>PMID:9730811</ref>. | '''Synaptotagmin''' (SYT) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen SYTs have been identified in mammals<ref>PMID:18468511</ref>. '''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions<ref>PMID:19412166</ref>. The C2A domain of SYT binds phospholipids in Ca+2-dpendent manner<ref>PMID:9730811</ref>. The C2B domain of SYT promotes binding to other C2B domains and to accessory proteins. Ca+2 binding causes intramolecular association of domains C2A and C2B. The synaptic fusion apparatus includes the affinity between SYT and [[Syntaxin]]-1, This affinity increases by ca. 2 orders of magnitude upon binding of Ca+2<ref>PMID:7559535</ref>. | ||
== Disease == | == Disease == | ||
== Relevance == | == Relevance == | ||
'''Synaptotagmin-4''' is up-regulated by chronic depolarization and seizures. '''Synaptotagmin-1''' is promising biomarker to monitor dysfunction and degeneration in Alzheimer disease<ref>PMID:27716408</ref>. | |||
== Structural highlights == | == Structural highlights == | ||
Revision as of 14:40, 3 December 2018
FunctionSynaptotagmin (SYT) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen SYTs have been identified in mammals[1]. Synaptotagmin-1 (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions[2]. The C2A domain of SYT binds phospholipids in Ca+2-dpendent manner[3]. The C2B domain of SYT promotes binding to other C2B domains and to accessory proteins. Ca+2 binding causes intramolecular association of domains C2A and C2B. The synaptic fusion apparatus includes the affinity between SYT and Syntaxin-1, This affinity increases by ca. 2 orders of magnitude upon binding of Ca+2[4]. DiseaseRelevanceSynaptotagmin-4 is up-regulated by chronic depolarization and seizures. Synaptotagmin-1 is promising biomarker to monitor dysfunction and degeneration in Alzheimer disease[5]. Structural highlightsAt the tip of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by 5 aspartates and one serine.
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3D structures of synaptotagmin3D structures of synaptotagmin
Updated on 03-December-2018
ReferencesReferences
- ↑ Hu ZT, Chen MR, Ping Z, Dong YM, Zhang RY, Xu T, Wu ZX. Synaptotagmin IV regulates dense core vesicle (DCV) release in LbetaT2 cells. Biochem Biophys Res Commun. 2008 Jul 11;371(4):781-6. doi:, 10.1016/j.bbrc.2008.04.174. Epub 2008 May 9. PMID:18468511 doi:http://dx.doi.org/10.1016/j.bbrc.2008.04.174
- ↑ Xu J, Pang ZP, Shin OH, Sudhof TC. Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nat Neurosci. 2009 Jun;12(6):759-66. doi: 10.1038/nn.2320. PMID:19412166 doi:http://dx.doi.org/10.1038/nn.2320
- ↑ Zhang X, Rizo J, Sudhof TC. Mechanism of phospholipid binding by the C2A-domain of synaptotagmin I. Biochemistry. 1998 Sep 8;37(36):12395-403. doi: 10.1021/bi9807512. PMID:9730811 doi:http://dx.doi.org/10.1021/bi9807512
- ↑ Chapman ER, Hanson PI, An S, Jahn R. Ca2+ regulates the interaction between synaptotagmin and syntaxin 1. J Biol Chem. 1995 Oct 6;270(40):23667-71. PMID:7559535
- ↑ Ohrfelt A, Brinkmalm A, Dumurgier J, Brinkmalm G, Hansson O, Zetterberg H, Bouaziz-Amar E, Hugon J, Paquet C, Blennow K. The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease. Alzheimers Res Ther. 2016 Oct 3;8(1):41. doi: 10.1186/s13195-016-0208-8. PMID:27716408 doi:http://dx.doi.org/10.1186/s13195-016-0208-8