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

Irina Dulubova, Xuelin Lou, Jun Lu, Iryna Huryeva, Amer Alam, Ralf Schneggenburger, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

α-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 α-RIM N-terminal sequence also binds to Rab3s (small synaptic vesicle GTPases), an interaction that regulates presynaptic plasticity. We now demonstrate that α-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 α-RIM zinc-finger domain. Elucidation of the three-dimensional structure of this domain by NMR spectroscopy facilitated the design of a mutation that abolishes α-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 α-RIMs, with nested binding sites for Rab3 and other targets, may be a general feature of Rab effectors that share homology with the α-RIM N-terminal sequence.

Original languageEnglish (US)
Pages (from-to)2839-2850
Number of pages12
JournalEMBO Journal
Volume24
Issue number16
DOIs
StatePublished - Aug 17 2005

Keywords

  • Munc13/unc13
  • Neurotransmitter release
  • Protein NMR
  • RIM
  • Rab proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Dulubova, I., Lou, X., Lu, J., Huryeva, I., Alam, A., Schneggenburger, R., Südhof, T. C., & Rizo-Rey, J. (2005). A Munc13/RIM/Rab3 tripartite complex: From priming to plasticity? EMBO Journal, 24(16), 2839-2850. https://doi.org/10.1038/sj.emboj.7600753