RIM1α is required for presynaptic long-term potentiation

Pablo E. Castillo, Susanne Schoch, Frank Schmitz, Thomas C. Südhof and Robert C. Malenka
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Pablo E. Castillo: Nancy Friend Pritzker Laboratory, Stanford University School of Medicine
Susanne Schoch: Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center
Frank Schmitz: Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center
Thomas C. Südhof: Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center
Robert C. Malenka: Nancy Friend Pritzker Laboratory, Stanford University School of Medicine

Nature, 2002, vol. 415, issue 6869, 327-330

Abstract: Abstract Two main forms of long-term potentiation (LTP)—a prominent model for the cellular mechanism of learning and memory—have been distinguished in the mammalian brain1. One requires activation of postsynaptic NMDA (N-methyl d-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses1,2, cerebellar parallel fibre synapses3,4 and corticothalamic synapses5, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP6, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable7,8. Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1α, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate9,10. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1α at the interface of synaptic vesicles and the active zone.

Date: 2002
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DOI: 10.1038/415327a

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