Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release
Open Access
- 27 April 2006
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 25 (10), 2039-2050
- https://doi.org/10.1038/sj.emboj.7601103
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.Keywords
This publication has 49 references indexed in Scilit:
- Different Effects on Fast Exocytosis Induced by Synaptotagmin 1 and 2 Isoforms and Abundance But Not by PhosphorylationJournal of Neuroscience, 2006
- Synaptotagmin I Synchronizes Transmitter Release in Mouse Hippocampal NeuronsJournal of Neuroscience, 2004
- Synaptotagmin Interaction with the Syntaxin/SNAP-25 Dimer Is Mediated by an Evolutionarily Conserved Motif and Is Sensitive to Inositol HexakisphosphatePublished by Elsevier ,2004
- Sr2+ Binding to the Ca2+ Binding Site of the Synaptotagmin 1 C2B Domain Triggers Fast Exocytosis without Stimulating SNARE InteractionsNeuron, 2003
- Transgenically Encoded Protein Photoinactivation (FlAsH-FALI)Neuron, 2002
- Deductive GenomicsAmerican Journal of PharmacoGenomics, 2002
- The tandem C2 domains of synaptotagmin contain redundant Ca2+ binding sites that cooperate to engage t-SNAREs and trigger exocytosisThe Journal of cell biology, 2001
- Definition of the Readily Releasable Pool of Vesicles at Hippocampal SynapsesNeuron, 1996
- Distinct Ca2+ and Sr2+ Binding Properties of SynaptotagminsPublished by Elsevier ,1995
- The effect on synaptic physiology of synaptotagmin mutations in drosophilaNeuron, 1994