Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming

Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner, We s how that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tetherin g, interact functionally. Disruption of this interaction causes a loss of f usion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficie nt neurons. RIM1 binding and Vesicle priming are mediated by two distinct s tructural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a f unctional link between synaptic vesicle tethering and priming, or it may re gulate the priming reaction itself, thereby determining the number of fusio n-competent vesicles.