1. Phosphatidylinositol 4,5-Bisphosphate Increases Ca2+ Affinity of Synaptotagmin-1 by 40-fold.
- Author
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van den Bogaart, Geert, Meyenberg, Karsten, Diederichsen, Ulf, and Jahn, Reinhard
- Subjects
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PHOSPHATIDYLINOSITOLS , *SYNAPTOTAGMINS , *EXOCYTOSIS , *THERMOPHORESIS , *NEUROTRANSMITTERS - Abstract
Synaptotagmin-1 is the main Ca2+ sensor of neuronal exocytosis. It binds to both Ca2+ and the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), but the precise cooperativity of this binding is still poorly understood. Here, we used microscale thermophoresis to quantify the cooperative binding of PIP2 and Ca2+ to synaptotagmin-1. We found that PIP2 bound to the well conserved polybasic patch of the C2B domain with an apparent dissociation constant of ~20 μm. PIP2 binding reduced the apparent dissociation constant for Ca2+ from ~250 to <5 μm. Thus, our data show that PIP2 makes synaptotagmin-1 >40-fold more sensitive to Ca2+. This interplay between Ca2+, synaptotagmin-1, and PIP2 is crucial for neurotransmitter release. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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