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

Geert van den Bogaart, K. Meyerberg, U. Diederichsen, Reinhard Jahn

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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.
Original languageEnglish
Pages (from-to)16447-16453
Number of pages7
JournalThe Journal of Biological Chemistry
Volume287
Issue number20
DOIs
Publication statusPublished - 11-May-2012
Externally publishedYes

Keywords

  • Phosphatidylinositol 4,5-bisphosphate
  • Ca2+ affinity
  • synaptotagmin-1
  • exocytosis
  • PIP(2)

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