PUBLICATION
Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release
- Authors
- Maximov, A., Shin, O.H., Liu, X., and Südhof, T.C.
- ID
- ZDB-PUB-090527-1
- Date
- 2007
- Source
- The Journal of cell biology 176(1): 113-24 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Phosphorylation/drug effects
- Calcium/metabolism
- Animals
- Cyclic AMP-Dependent Protein Kinases/metabolism
- Cyclic AMP/pharmacology
- Amino Acid Sequence
- Hippocampus/drug effects
- Hippocampus/ultrastructure
- Molecular Sequence Data
- Phosphoserine/metabolism
- Phosphoproteins/metabolism*
- Neurotransmitter Agents
- Protein Transport/drug effects
- Glycosylation/drug effects
- Synaptotagmins/chemistry
- Synaptotagmins/genetics
- Synaptotagmins/metabolism*
- Protein Binding/drug effects
- Gene Expression Profiling
- Rats
- Phospholipids/metabolism
- Mice
- Synaptic Vesicles/drug effects
- Synaptic Vesicles/metabolism*
- Synaptotagmin I/metabolism
- Inhibitory Postsynaptic Potentials/drug effects
- PubMed
- 17190793 Full text @ J. Cell Biol.
Citation
Maximov, A., Shin, O.H., Liu, X., and Südhof, T.C. (2007) Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release. The Journal of cell biology. 176(1):113-24.
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 Ca(2+). 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 serine(97) 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 Ca(2+)-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping