Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release

Anton Maximov, Ok Ho Shin, Xinran Liu, Thomas C. Südhof

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine 97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.

Original languageEnglish (US)
Pages (from-to)113-124
Number of pages12
JournalJournal of Cell Biology
Volume176
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Synaptotagmins
Synaptic Vesicles
Phosphoproteins
Neurotransmitter Agents
Cyclic AMP-Dependent Protein Kinases
Synaptotagmin I
Protein Isoforms
Phosphorylation
SNARE Proteins
Exocytosis
Alanine
Synapses
Serine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release. / Maximov, Anton; Shin, Ok Ho; Liu, Xinran; Südhof, Thomas C.

In: Journal of Cell Biology, Vol. 176, No. 1, 01.01.2007, p. 113-124.

Research output: Contribution to journalArticle

Maximov, Anton ; Shin, Ok Ho ; Liu, Xinran ; Südhof, Thomas C. / Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release. In: Journal of Cell Biology. 2007 ; Vol. 176, No. 1. pp. 113-124.
@article{3c3b036fb4e5473e82b60fe031d33ef3,
title = "Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release",
abstract = "Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine 97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.",
author = "Anton Maximov and Shin, {Ok Ho} and Xinran Liu and S{\"u}dhof, {Thomas C.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1083/jcb.200607021",
language = "English (US)",
volume = "176",
pages = "113--124",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "1",

}

TY - JOUR

T1 - Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release

AU - Maximov, Anton

AU - Shin, Ok Ho

AU - Liu, Xinran

AU - Südhof, Thomas C.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine 97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.

AB - Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine 97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.

UR - http://www.scopus.com/inward/record.url?scp=33846020920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846020920&partnerID=8YFLogxK

U2 - 10.1083/jcb.200607021

DO - 10.1083/jcb.200607021

M3 - Article

C2 - 17190793

AN - SCOPUS:33846020920

VL - 176

SP - 113

EP - 124

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 1

ER -