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

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van den Bogaart,  G.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Jahn,  R.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Citation

van den Bogaart, G., Meyenberg, K., Diederichsen, U., & Jahn, R. (2012). Phosphatidylinositol 4,5-bisphosphate increases the Ca2+ affinity of synaptotagmin-1 40-fold. Journal of Biological Chemistry, 287(20), 16447-16453. doi:10.1074/jbc.M112.343418.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-84C3-1
Abstract
Synaptotagmin-1 is the main Ca 2+ - s ensor of neuronal exocytosis. It binds to both Ca 2+ and the anionic phospholipid p hosphatidylinositol 4,5-bisphosphate (PIP2), but the precise cooperativity of this binding is still poorly understood. Here, we used microscale thermophoresis (MST) to quantify the cooperative binding of PIP2 and Ca 2+ to s ynaptotagmin-1. We find that PIP2 binds to the well-conserved polybasic patch of the C2B-domain with an apparent dissociation constant of ~20 μM. PIP2-binding reduces the apparent dissociation constant for Ca 2+ from ~ 250 μM to < 5 μM. Thus, our data show that PIP2 makes synaptotagmin-1 > 40-fold more sensitive for Ca 2+ . This interplay between C a 2+ , synaptotagmin-1 and PIP2 is crucial for n eurotransmitter release.