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

A Betz, P Thakur, HJ Junge, U Ashery, JS Rhee… - Neuron, 2001 - cell.com
A Betz, P Thakur, HJ Junge, U Ashery, JS Rhee, V Scheuss, C Rosenmund, J Rettig
Neuron, 2001cell.com
Synaptic neurotransmitter release is restricted to active zones, where the processes of
synaptic vesicle tethering, priming to fusion competence, and Ca 2+-triggered fusion are
taking place in a highly coordinated manner. We show that the active zone components
Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative
role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of
fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons …
Abstract
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 show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
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