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| Subject Categories: Neuroscience |
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| The EMBO Journal
(2006) 25, 5852–5863, doi:10.1038/sj.emboj.7601425 Published online 23 November 2006 |
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Redundant functions of RIM1 and RIM2 in Ca2+-triggered neurotransmitter release |
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| Susanne Schoch1, 2, 3, Tobias Mittelstaedt1, Pascal S Kaeser2, Daniel Padgett2, Nicole Feldmann1, 8, Vivien Chevaleyre4, Pablo E Castillo4, Robert E Hammer5, Weiping Han2, 9, Frank Schmitz6, Weichun Lin2 and Thomas C Südhof2, 3, 7 |
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1 Emmy Noether Research Group, Institute of Neuropathology, Department of Epileptology, University Bonn, Bonn, Germany 2 Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA 3 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA 4 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA 5 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA 6 Institute of Anatomy and Cell Biology, Universität des Saarlandes, Homburg, Germany 7 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA To whom correspondence should be addressed Susanne Schoch, Emmy Noether Research Group, Institute of Neuropathology, Department of Epileptology, University Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. Tel.: +49 228 287 19109; Fax: +49 228 287 19110; E-mail: susanne.schoch@uni-bonn.de 8 Present address: Department of Cell Physiology and Metabolism, University Medical Center, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland 9 Present address: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore 138667, Singapore Received 11 April 2006; Accepted 13 October 2006; Published online 23 November 2006. |
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| Abstract |
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| -RIMs (RIM1 and RIM2) are multidomain active zone proteins of presynaptic terminals. -RIMs bind to Rab3 on synaptic vesicles and to Munc13 on the active zone via their N-terminal region, and interact with other synaptic proteins via their central and C-terminal regions. Although RIM1 has been well characterized, nothing is known about the function of RIM2. We now show that RIM1 and RIM2 are expressed in overlapping but distinct patterns throughout the brain. To examine and compare their functions, we generated knockout mice lacking RIM2, and crossed them with previously produced RIM1 knockout mice. We found that deletion of either RIM1 or RIM2 is not lethal, but ablation of both -RIMs causes postnatal death. This lethality is not due to a loss of synapse structure or a developmental change, but to a defect in neurotransmitter release. Synapses without -RIMs still contain active zones and release neurotransmitters, but are unable to mediate normal Ca2+-triggered release. Our data thus demonstrate that -RIMs are not essential for synapse formation or synaptic exocytosis, but are required for normal Ca2+-triggering of exocytosis. |
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| Keywords: active zone, neurotransmitter release, RIM, synapse, synaptic plasticity |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHRedundant functions of RIM1α and RIM2α in Ca 2+ -triggered neurotransmitter release The EMBO Journal Article Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion The EMBO Journal Article (21 Jun 2006) Rab-αGDI activity is regulated by a Hsp90 chaperone complex The EMBO Journal Article (15 Nov 2002) Genetic analysis of synaptotagmin 2 in spontaneous and Ca 2+ -triggered neurotransmitter release The EMBO Journal Article (17 May 2006) |
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