Medical College of Wisconsin
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A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity? EMBO J 2005 Aug 17;24(16):2839-50

Date

07/30/2005

Pubmed ID

16052212

Pubmed Central ID

PMC1187938

DOI

10.1038/sj.emboj.7600753

Scopus ID

2-s2.0-28844449520 (requires institutional sign-in at Scopus site)   212 Citations

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.

Author List

Dulubova I, Lou X, Lu J, Huryeva I, Alam A, Schneggenburger R, Südhof TC, Rizo J

Author

Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Binding Sites
Calorimetry
Electrophysiology
Escherichia coli
GTP-Binding Proteins
Glutathione Transferase
Humans
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes
Mutagenesis
Nerve Tissue Proteins
Nuclear Magnetic Resonance, Biomolecular
Sequence Alignment
Synaptic Vesicles
rab3 GTP-Binding Proteins