A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?

EMBO J. 2005 Aug 17;24(16):2839-50. doi: 10.1038/sj.emboj.7600753. Epub 2005 Jul 28.


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 types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Rim protein, mammalian
  • UNC13B protein, human
  • Glutathione Transferase
  • GTP-Binding Proteins
  • rab3 GTP-Binding Proteins