Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release

J Cell Biol. 2004 Jan 19;164(2):301-11. doi: 10.1083/jcb.200307101.


We have recently isolated a novel cytomatrix at the active zone (CAZ)-associated protein, CAST, and found it directly binds another CAZ protein RIM1 and indirectly binds Munc13-1 through RIM1; RIM1 and Munc13-1 directly bind to each other and are implicated in priming of synaptic vesicles. Here, we show that all the CAZ proteins thus far known form a large molecular complex in the brain, including CAST, RIM1, Munc13-1, Bassoon, and Piccolo. RIM1 and Bassoon directly bind to the COOH terminus and central region of CAST, respectively, forming a ternary complex. Piccolo, which is structurally related to Bassoon, also binds to the Bassoon-binding region of CAST. Moreover, the microinjected RIM1- or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. Furthermore, the CAST-binding domain of RIM1 or Bassoon also impairs synaptic transmission in the cultured neurons. These results indicate that CAST serves as a key component of the CAZ structure and is involved in neurotransmitter release by binding these CAZ proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain / physiology
  • Cells, Cultured
  • Cloning, Molecular
  • Cytoskeletal Proteins
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • Hippocampus / physiology
  • Kinetics
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / physiology*
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / physiology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Recombinant Proteins / metabolism
  • Superior Cervical Ganglion / physiology
  • Synapses / physiology
  • Transfection
  • Zinc Fingers


  • Adaptor Proteins, Signal Transducing
  • Bsn protein, rat
  • Cytoskeletal Proteins
  • ERC2 protein, human
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • RIMS1 protein, human
  • Recombinant Proteins
  • Rim protein, mammalian
  • Rims1 protein, rat
  • GTP-Binding Proteins