RGD Reference Report - The importance of an asymmetric distribution of acidic lipids for synaptotagmin 1 function as a Ca2+ sensor. - Rat Genome Database

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The importance of an asymmetric distribution of acidic lipids for synaptotagmin 1 function as a Ca2+ sensor.

Authors: Lai, Y  Shin, YK 
Citation: Lai Y and Shin YK, Biochem J. 2012 Apr 1;443(1):223-9. doi: 10.1042/BJ20112044.
RGD ID: 7205654
Pubmed: PMID:22229667   (View Abstract at PubMed)
PMCID: PMC4412275   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20112044   (Journal Full-text)

Syt1 (synaptotagmin 1) is a major Ca2+ sensor for synaptic vesicle fusion. Although Syt1 is known to bind to SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) complexes and to the membrane, the mechanism by which Syt1 regulates vesicle fusion is controversial. In the present study we used in vitro lipid-mixing assays to investigate the Ca2+-dependent Syt1 function in proteoliposome fusion. To study the role of acidic lipids, the concentration of negatively charged DOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine) in the vesicle was varied. Syt1 stimulated lipid mixing by 3-10-fold without Ca2+. However, with Ca2+ there was an additional 2-5-fold enhancement. This Ca2+-dependent stimulation was observed only when there was excess PS (phosphatidylserine) on the t-SNARE (target SNARE) side. If there was equal or more PS on the v-SNARE (vesicule SNARE) side the Ca2+-dependent stimulation was not observed. We found that Ca2+ at a concentration between 10 and 50 muM was sufficient to give rise to the maximal enhancement. The single-vesicle-fusion assay indicates that the Ca2+-dependent enhancement was mainly on docking, whereas its effect on lipid mixing was small. Thus for Syt1 to function as a Ca2+ sensor, a charge asymmetry appears to be important and this may play a role in steering Syt1 to productively trans bind to the plasma membrane.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Syt1Ratdetection of calcium ion  IDA  RGD 
Syt1Ratvesicle docking  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Syt1  (synaptotagmin 1)

Additional Information