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PMID: 16642042 Published · ppublish English Journal Article

Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release.

The EMBO journal ·Vol. 25 ·No. 10 ·2006-05-17 ·Pages 2039-50

Pang ZP, Sun J, Rizo J, Maximov A, Südhof TC

Abstract

Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca2+-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca2+ triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca2+ triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling 'release slots' for synaptic vesicles at the active zone.

MeSH Terms
Action Potentials/physiology Amino Acid Sequence Animals Ataxia/genetics,metabolism Brain/anatomy & histology Calcium/metabolism In Vitro Techniques Mice Molecular Sequence Data Neurons/cytology,metabolism Neurotransmitter Agents/metabolism Patch-Clamp Techniques Point Mutation Protein Denaturation Protein Structure, Tertiary Sequence Alignment Synapses/metabolism Synaptic Transmission/physiology Synaptotagmin I/genetics,metabolism Synaptotagmin II/genetics,metabolism
Chemicals
Neurotransmitter Agents Synaptotagmin I Synaptotagmin II Syt1 protein, mouse Syt2 protein, mouse Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pang Zhiping P
Department of Molecular Genetics, Center for Basic Neuroscience, Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Sun Jianyuan
Rizo Josep
Maximov Anton
Südhof Thomas C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601103
Published
2006-05-17
Epub
2006-00-27
Pages
2039-50
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1462977
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601103 PMC Full Text View journal details
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