RGD Reference Report - Rat and Drosophila synaptotagmin 4 have opposite effects during SNARE-catalyzed membrane fusion. - Rat Genome Database

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Rat and Drosophila synaptotagmin 4 have opposite effects during SNARE-catalyzed membrane fusion.

Authors: Wang, Z  Chapman, ER 
Citation: Wang Z and Chapman ER, J Biol Chem. 2010 Oct 1;285(40):30759-66. doi: 10.1074/jbc.M110.137745. Epub 2010 Aug 5.
RGD ID: 11535104
Pubmed: PMID:20688915   (View Abstract at PubMed)
PMCID: PMC2945570   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.137745   (Journal Full-text)

Synaptotagmins (Syt) are a large family of proteins that regulate membrane traffic in neurons and other cell types. One isoform that has received considerable attention is SYT4, with apparently contradictory reports concerning the function of this isoform in fruit flies and mice. SYT4 was reported to function as a negative regulator of neurotrophin secretion in mouse neurons and as a positive regulator of secretion of a yet to be identified growth factor from muscle cells in flies. Here, we have directly compared the biochemical and functional properties of rat and fly SYT4. We report that rat SYT4 inhibited SNARE-catalyzed membrane fusion in both the absence and presence of Ca(2+). In marked contrast, fly SYT4 stimulated SNARE-mediated membrane fusion in response to Ca(2+). Analysis of chimeric molecules, isolated C2 domains, and point mutants revealed that the C2B domain of the fly protein senses Ca(2+) and is sufficient to stimulate fusion. Rat SYT4 was able to stimulate fusion in response to Ca(2+) when the conserved Asp-to-Ser Ca(2+) ligand substitution in its C2A domain was reversed. In summary, rat SYT4 serves as an inhibitory isoform, whereas fly SYT4 is a bona fide Ca(2+) sensor capable of coupling Ca(2+) to membrane fusion.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of vesicle fusion involved_inIDA 11535104PMID:20688915ParkinsonsUK-UCL 
positive regulation of vesicle fusion involved_inIDA 11535104PMID:20688915ParkinsonsUK-UCL 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Snap25  (synaptosome associated protein 25)
Stx1a  (syntaxin 1A)
Syt1  (synaptotagmin 1)
Syt4  (synaptotagmin 4)


Additional Information