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Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold.

Authors: Van den Bogaart, G  Meyenberg, K  Diederichsen, U  Jahn, R 
Citation: van den Bogaart G, etal., J Biol Chem. 2012 May 11;287(20):16447-53. doi: 10.1074/jbc.M112.343418. Epub 2012 Mar 23.
Pubmed: (View Article at PubMed) PMID:22447935
DOI: Full-text: DOI:10.1074/jbc.M112.343418

Synaptotagmin-1 is the main Ca(2+) sensor of neuronal exocytosis. It binds to both Ca(2+) and the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)), but the precise cooperativity of this binding is still poorly understood. Here, we used microscale thermophoresis to quantify the cooperative binding of PIP(2) and Ca(2+) to synaptotagmin-1. We found that PIP(2) bound to the well conserved polybasic patch of the C2B domain with an apparent dissociation constant of approximately 20 muM. PIP(2) binding reduced the apparent dissociation constant for Ca(2+) from approximately 250 to <5 muM. Thus, our data show that PIP(2) makes synaptotagmin-1 >40-fold more sensitive to Ca(2+). This interplay between Ca(2+), synaptotagmin-1, and PIP(2) is crucial for neurotransmitter release.

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RGD Object Information
RGD ID: 7205653
Created: 2013-01-10
Species: All species
Last Modified: 2013-01-10
Status: ACTIVE



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