Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming

Neuron. 2001 Apr;30(1):183-96. doi: 10.1016/s0896-6273(01)00272-0.


Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Binding Sites / genetics
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Sequence Homology, Amino Acid
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*
  • Two-Hybrid System Techniques
  • Zinc Fingers / physiology
  • rab3A GTP-Binding Protein / metabolism


  • DNA-Binding Proteins
  • Fungal Proteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Protein Isoforms
  • Unc13a protein, rat
  • rab3A GTP-Binding Protein

Associated data

  • GENBANK/AF159706