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

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.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Brain, Cells, Cultured, Cloning, Molecular, GTP-Binding Proteins, Hippocampus, Kinetics, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neurotransmitter Agents, Peptide Fragments, Proto-Oncogene Proteins, Rats, Recombinant Proteins, Superior Cervical Ganglion, Synapses, Transfection, Zinc Fingers
J. Cell Biol.
Date: Jan. 19, 2004
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