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PMID: 22447935 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of biological chemistry ·Vol. 287 ·No. 20 ·2012-05-11 ·Pages 16447-53

van den Bogaart G, Meyenberg K, Diederichsen U, Jahn R

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.

MeSH Terms
Animals Calcium/chemistry,metabolism Neurotransmitter Agents/metabolism Phosphatidylinositol 4,5-Diphosphate/chemistry,metabolism Protein Binding Protein Structure, Tertiary Rats Synaptotagmin I/chemistry,genetics,metabolism
Chemicals
Neurotransmitter Agents Phosphatidylinositol 4,5-Diphosphate Synaptotagmin I Syt1 protein, rat Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
van den Bogaart Geert
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Georg-August University, 37077 Göttingen, Germany.
Meyenberg Karsten
Diederichsen Ulf
Jahn Reinhard
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M112.343418
Published
2012-05-11
Epub
2012-00-23
Pages
16447-53
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3351315
Subset
IM
Grants
NIGMS NIH HHS · P01 GM072694 · United States
External Links
PubMed source DOI: 10.1074/jbc.M112.343418 PMC Full Text View journal details
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