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  • The EMBO Journal (2006) 25, 5852 - 5863
  • doi:10.1038/sj.emboj.7601425

Published online: 23 November 2006

Redundant functions of RIM1alpha and RIM2alpha in Ca2+-triggered neurotransmitter release

Susanne Schoch1,2,3, Tobias Mittelstaedt1, Pascal S Kaeser2, Daniel Padgett2, Nicole Feldmann1,a, Vivien Chevaleyre4, Pablo E Castillo4, Robert E Hammer5, Weiping Han2,b, Frank Schmitz6, Weichun Lin2 and Thomas C Südhof2,3,7

  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

Correspondence to:

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

aPresent address: Department of Cell Physiology and Metabolism, University Medical Center, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland

bPresent address: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore 138667, Singapore

Received 11 April 2006; Accepted 13 October 2006

alpha-RIMs (RIM1alpha and RIM2alpha) are multidomain active zone proteins of presynaptic terminals. alpha-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 RIM1alpha has been well characterized, nothing is known about the function of RIM2alpha. We now show that RIM1alpha and RIM2alpha are expressed in overlapping but distinct patterns throughout the brain. To examine and compare their functions, we generated knockout mice lacking RIM2alpha, and crossed them with previously produced RIM1alpha knockout mice. We found that deletion of either RIM1alpha or RIM2alpha is not lethal, but ablation of both alpha-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 alpha-RIMs still contain active zones and release neurotransmitters, but are unable to mediate normal Ca2+-triggered release. Our data thus demonstrate that alpha-RIMs are not essential for synapse formation or synaptic exocytosis, but are required for normal Ca2+-triggering of exocytosis.

  • Keywords:

    • active zone,
    • neurotransmitter release,
    • RIM,
    • synapse,
    • synaptic plasticity