Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold |
| |
Authors: | van den Bogaart Geert Meyenberg Karsten Diederichsen Ulf Jahn Reinhard |
| |
Institution: | From the ?Department of Neurobiology, Max Planck Institute for Biophysical Chemistry and ;the §Institute for Organic and Biomolecular 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. |
| |
Keywords: | Calcium-binding Proteins Lipid-binding Protein Neurobiology Phosphatidylinositol Synaptotagmin Thermodynamics Thermophoresis |
本文献已被 PubMed 等数据库收录! |
|