RIM C2B Domains Target Presynaptic Active Zone Functions to PIP2-Containing Membranes

Arthur P.H. de Jong, Carlos M. Roggero, Meng Ru Ho, Man Yan Wong, Chad A Brautigam, Jose Rizo-Rey, Pascal S. Kaeser

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Rapid and efficient synaptic vesicle fusion requires a pool of primed vesicles, the nearby tethering of Ca2+ channels, and the presence of the phospholipid PIP2 in the target membrane. Although the presynaptic active zone mediates the first two requirements, it is unclear how fusion is targeted to membranes with high PIP2 content. Here we find that the C2B domain of the active zone scaffold RIM is critical for action potential-triggered fusion. Remarkably, the known RIM functions in vesicle priming and Ca2+ influx do not require RIM C2B domains. Instead, biophysical experiments reveal that RIM C2 domains, which lack Ca2+ binding, specifically bind to PIP2. Mutational analyses establish that PIP2 binding to RIM C2B and its tethering to the other RIM domains are crucial for efficient exocytosis. We propose that RIM C2B domains are constitutive PIP2-binding modules that couple mechanisms for vesicle priming and Ca2+ channel tethering to PIP2-containing target membranes. de Jong et al. demonstrate that the RIM C2B domain is important for neurotransmitter release. RIM C2B binds to the phospholipid PIP2, and this interaction directs synaptic vesicle priming and Ca2+ influx to the PIP2-containing plasma membrane for efficient exocytosis.

Original languageEnglish (US)
JournalNeuron
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • active zone
  • C2 domain
  • neurotransmitter release
  • PIP
  • RIM
  • secretion
  • synaptic vesicle

ASJC Scopus subject areas

  • Neuroscience(all)

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