Phosphatidylinositol 4,5-bisphosphate Increases Ca2+ Affinity of Synaptotagmin-1 by 40-fold

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Mar 27

PMID 22447935

Citations 74

Authors

Geert van den Bogaart

Karsten Meyenberg

Ulf Diederichsen

Reinhard Jahn

Affiliations

Soon will be listed here.

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.

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