Synaptotagmin: Difference between revisions

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== Function ==
== Function ==


'''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-dependent 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>.  
'''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-dependent 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>.  
'''Synaptotagmin-like proteins''' (SYTL) are required in a generation of a single apical surface per cell<ref>PMID:22820376</ref>.
'''Synaptotagmin-like proteins''' (SYTL) are required in a generation of a single apical surface per cell<ref>PMID:22820376</ref>.


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== Structural highlights ==
== Structural highlights ==


SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the <scene name='80/802718/Cv/7'>C2A Ca+2-binding, C2B</scene>, spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates<ref>PMID:24373768</ref>.
SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the <scene name='80/802718/Cv/12'>C2A Ca+2-binding, C2B</scene>, spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates<ref>PMID:24373768</ref>.
*<scene name='80/802718/Cv/8'>1st Ca+2 binding site</scene>. Water molecules are shown as red spheres.
*<scene name='80/802718/Cv/8'>1st Ca+2 binding site</scene>. Water molecules are shown as red spheres.
*<scene name='80/802718/Cv/9'>2nd Ca+2 binding site</scene>.
*<scene name='80/802718/Cv/9'>2nd Ca+2 binding site</scene>.

Revision as of 16:46, 23 November 2020

Function

Synaptotagmin (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-dependent 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].

Synaptotagmin-like proteins (SYTL) are required in a generation of a single apical surface per cell[5].

Relevance

Synaptotagmin-4 is up-regulated by chronic depolarization and seizures. Synaptotagmin-1 is a promising biomarker to monitor dysfunction and degeneration in Alzheimer disease[6].

Structural highlights

SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the , spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates[7].

  • . Water molecules are shown as red spheres.
  • .
  • .
  • .

3D structures of synaptotagmin

Synaptotagmin 3D structures


Synaptostagmin-2 C2A and C2B domains complex with Ca+2 ions (green) (PDB code 4npk)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Galvez-Santisteban M, Rodriguez-Fraticelli AE, Bryant DM, Vergarajauregui S, Yasuda T, Banon-Rodriguez I, Bernascone I, Datta A, Spivak N, Young K, Slim CL, Brakeman PR, Fukuda M, Mostov KE, Martin-Belmonte F. Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nat Cell Biol. 2012 Aug;14(8):838-49. doi: 10.1038/ncb2541. Epub 2012 Jul 22. PMID:22820376 doi:http://dx.doi.org/10.1038/ncb2541
  6. ↑ 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
  7. ↑ Xu J, Bacaj T, Zhou A, Tomchick DR, Sudhof TC, Rizo J. Structure and Ca-Binding Properties of the Tandem C Domains of E-Syt2. Structure. 2013 Dec 24. pii: S0969-2126(13)00461-9. doi:, 10.1016/j.str.2013.11.011. PMID:24373768 doi:http://dx.doi.org/10.1016/j.str.2013.11.011

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