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RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone

Author

Listed:
  • Susanne Schoch

    (Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center)

  • Pablo E. Castillo

    (Nancy Friend Pritzker Laboratory, Stanford University School of Medicine
    Albert Einstein College of Medicine, Bronx)

  • Tobias Jo

    (Max-Planck-Institut für experimentelle Medizin)

  • Konark Mukherjee

    (Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center)

  • Martin Geppert

    (Max-Planck-Institut für experimentelle Medizin
    Pharmacia Corporation)

  • Yun Wang

    (Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center)

  • Frank Schmitz

    (Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center
    Leibniz Institut für Neurobiologie)

  • Robert C. Malenka

    (Nancy Friend Pritzker Laboratory, Stanford University School of Medicine)

  • Thomas C. Südhof

    (Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center)

Abstract

Neurotransmitters are released by synaptic vesicle fusion at the active zone1,2. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood3. Here we show that RIM1α, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A4,5, interacts with several active zone molecules, including Munc13-1 (ref. 6) and α-liprins7,8, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1α in mice shows that RIM1α is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1α has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.

Suggested Citation

  • Susanne Schoch & Pablo E. Castillo & Tobias Jo & Konark Mukherjee & Martin Geppert & Yun Wang & Frank Schmitz & Robert C. Malenka & Thomas C. Südhof, 2002. "RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone," Nature, Nature, vol. 415(6869), pages 321-326, January.
    • Handle: RePEc:nat:nature:v:415:y:2002:i:6869:d:10.1038_415321a
    DOI: 10.1038/415321a
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    Cited by:

    1. Natalie J. Guzikowski & Ege T. Kavalali, 2024. "Functional specificity of liquid-liquid phase separation at the synapse," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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