RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of munc13

Lunbin Deng, Pascal S. Kaeser, Wei Xu, Thomas C. Südhof

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

At a synapse, the presynaptic active zone mediates synaptic vesicle exocytosis. RIM proteins are active zone scaffolding molecules that-among others-mediate vesicle priming and directly or indirectly interact with most other essential presynaptic proteins. In particular, the Zn2+ finger domain of RIMs binds to the C2A domain of the priming factor Munc13, which forms a homodimer in the absence of RIM but a heterodimer with it. Here, we show that RIMs mediate vesicle priming not by coupling Munc13 to other active zone proteins as thought but by directly activating Munc13. Specifically, we found that the isolated Zn2+ finger domain of RIMs autonomously promoted vesicle priming by binding to Munc13, thereby relieving Munc13 homodimerization. Strikingly, constitutively monomeric mutants of Munc13 rescued priming in RIM-deficient synapses, whereas wild-type Munc13 did not. Both mutant and wild-type Munc13, however, rescued priming in Munc13-deficient synapses. Thus, homodimerization of Munc13 inhibits its priming function, and RIMs activate priming by disrupting Munc13 homodimerization.

Original languageEnglish (US)
Pages (from-to)317-331
Number of pages15
JournalNeuron
Volume69
Issue number2
DOIs
StatePublished - Jan 27 2011

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Synapses
Fingers
Proteins
Synaptic Vesicles
Exocytosis

ASJC Scopus subject areas

  • Neuroscience(all)

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RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of munc13. / Deng, Lunbin; Kaeser, Pascal S.; Xu, Wei; Südhof, Thomas C.

In: Neuron, Vol. 69, No. 2, 27.01.2011, p. 317-331.

Research output: Contribution to journalArticle

Deng, Lunbin ; Kaeser, Pascal S. ; Xu, Wei ; Südhof, Thomas C. / RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of munc13. In: Neuron. 2011 ; Vol. 69, No. 2. pp. 317-331.
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