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J Biol Chem. 2012 May 11;287(20):16447-53. doi: 10.1074/jbc.M112.343418. Epub 2012 Mar 23.

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

Author information

1
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Georg-August University, 37077 Göttingen, Germany.

Abstract

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 ∼20 μM. PIP(2) binding reduced the apparent dissociation constant for Ca(2+) from ∼250 to <5 μM. 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.

PMID:
22447935
PMCID:
PMC3351315
DOI:
10.1074/jbc.M112.343418
[Indexed for MEDLINE]
Free PMC Article

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