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 language | English (US) |
---|---|
Pages (from-to) | 335-349.e7 |
Journal | Neuron |
Volume | 98 |
Issue number | 2 |
DOIs | |
State | Published - Apr 18 2018 |
Keywords
- C2 domain
- PIP
- RIM
- active zone
- neurotransmitter release
- secretion
- synaptic vesicle
ASJC Scopus subject areas
- General Neuroscience