RIM C 2 B Domains Target Presynaptic Active Zone Functions to PIP 2 -Containing Membranes

DE JONG, ARTHUR P.H.; ROGGERO, CARLOS M.; HO, MENG-RU; WONG, MAN YAN; BRAUTIGAM, CHAD A.; RIZO, JOSEP; KAESER, PASCAL S.

NEURON

CELL PRESS

Año: 2018 vol. 98 p. 335 - 349

0896-6273

Rapid and efficient synaptic vesicle fusion requires apool of primed vesicles, the nearby tethering of Ca2+channels, and the presence of the phospholipid PIP2in the target membrane. Although the presynapticactive zone mediates the first two requirements, itis unclear how fusion is targeted to membraneswith high PIP2 content. Here we find that the C2Bdomain of the active zone scaffold RIM is critical foraction potential-triggered fusion. Remarkably, theknown RIM functions in vesicle priming and Ca2+influx do not require RIM C2B domains. Instead, biophysicalexperiments reveal that RIM C2 domains,which lack Ca2+ binding, specifically bind to PIP2.Mutational analyses establish that PIP2 binding toRIM C2B and its tethering to the other RIM domainsare crucial for efficient exocytosis. We propose thatRIM C2B domains are constitutive PIP2-bindingmodulesthat couple mechanisms for vesicle priming andCa2+ channel tethering to PIP2-containing targetmembranes.