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- Title
A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
- Authors
Dulubova, Irina; Lou, Xuelin; Lu, Jun; Huryeva, Iryna; Alam, Amer; Schneggenburger, Ralf; Südhof, Thomas C; Rizo, Josep
- Abstract
alpha-RIMs and Munc13s are active zone proteins that control priming of synaptic vesicles to a readily releasable state, and interact with each other via their N-terminal sequences. The alpha-RIM N-terminal sequence also binds to Rab3s (small synaptic vesicle GTPases), an interaction that regulates presynaptic plasticity. We now demonstrate that alpha-RIMs contain adjacent but separate Munc13- and Rab3-binding sites, allowing formation of a tripartite Rab3/RIM/Munc13 complex. Munc13 binding is mediated by the alpha-RIM zinc-finger domain. Elucidation of the three-dimensional structure of this domain by NMR spectroscopy facilitated the design of a mutation that abolishes alpha-RIM/Munc13 binding. Selective disruption of this interaction in the calyx of Held synapse decreased the size of the readily releasable vesicle pool. Our data suggest that the ternary Rab3/RIM/Munc13 interaction approximates synaptic vesicles to the priming machinery, providing a substrate for presynaptic plasticity. The modular architecture of alpha-RIMs, with nested binding sites for Rab3 and other targets, may be a general feature of Rab effectors that share homology with the alpha-RIM N-terminal sequence.
- Publication
The EMBO journal, 2005, Vol 24, Issue 16, p2839
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7600753