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| Content Provider | PubMed Central |
|---|---|
| Author | Irina, Dulubova Lou, Xuelin Lu, Jun Huryeva, Iryna Alam, Amer Ralf, Schneggenburger Südhof, Thomas C. Rizo, Josep |
| Copyright Year | 2005 |
| 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. |
| Related Links | http://dx.doi.org/10.1038/sj.emboj.7600753 |
| Ending Page | 2850 |
| Page Count | 12 |
| Starting Page | 2839 |
| File Format | |
| ISSN | 02614189 |
| e-ISSN | 14602075 |
| Journal | The EMBO Journal |
| Issue Number | 16 |
| Volume Number | 24 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2005-07-01 |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Molecular Biology |
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