RIM C 2 B Domains Target Presynaptic Active Zone Functions to PIP 2 -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 journalArticlepeer-review

20 Scopus citations

Abstract

Rapid and efficient synaptic vesicle fusion requires a pool of primed vesicles, the nearby tethering of Ca 2+ channels, and the presence of the phospholipid PIP 2 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 PIP 2 content. Here we find that the C 2 B domain of the active zone scaffold RIM is critical for action potential-triggered fusion. Remarkably, the known RIM functions in vesicle priming and Ca 2+ influx do not require RIM C 2 B domains. Instead, biophysical experiments reveal that RIM C 2 domains, which lack Ca 2+ binding, specifically bind to PIP 2 . Mutational analyses establish that PIP 2 binding to RIM C 2 B and its tethering to the other RIM domains are crucial for efficient exocytosis. We propose that RIM C 2 B domains are constitutive PIP 2 -binding modules that couple mechanisms for vesicle priming and Ca 2+ channel tethering to PIP 2 -containing target membranes. de Jong et al. demonstrate that the RIM C 2 B domain is important for neurotransmitter release. RIM C 2 B binds to the phospholipid PIP 2 , and this interaction directs synaptic vesicle priming and Ca 2+ influx to the PIP 2 -containing plasma membrane for efficient exocytosis.

Original languageEnglish (US)
Pages (from-to)335-349.e7
JournalNeuron
Volume98
Issue number2
DOIs
StatePublished - Apr 18 2018

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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