A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
EMBO J
; 24(16): 2839-50, 2005 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-16052212
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
/
Modelos Moleculares
/
Proteínas de Ligação ao GTP
/
Proteínas rab3 de Ligação ao GTP
/
Complexos Multiproteicos
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article