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Role of the Doc2α -Munc13-1 Interaction in the Neurotransmitter Release Process
Sumiko Mochida, Satoshi Orita, Gaku Sakaguchi, Takuya Sasaki and Yoshimi Takai
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 19 (Sep. 15, 1998), pp. 11418-11422
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/46322
Page Count: 5
You can always find the topics here!Topics: Neurons, Synaptic transmission, Neurotransmitters, Synapses, Action potentials, Pipettes, Amino acids, Proteins, Cell membranes, Plasma interactions
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Doc2α and Munc13-1 proteins are highly concentrated on synaptic vesicles and the presynaptic plasma membrane, respectively, and have been implicated in Ca2+-dependent neurotransmitter release. Doc2α interacts with Munc13-1 through the N-terminal region of Doc2α (the Mid domain; amino acid residues 13-37). Here we examine whether the interaction between Doc2α and Munc13-1 is required for Ca2+-dependent neurotransmitter release from intact neuron. A synthetic Mid peptide (the Mid peptide), but not a control mutated Mid peptide or a scrambled Mid peptide, inhibited the interaction between Doc2α and Munc13-1 in vitro. Introduction of the Mid peptide into presynaptic neurons of cholinergic synapses, formed between rat superior cervical ganglion neurons, reversibly inhibited synaptic transmission evoked by action potentials. In contrast, the control peptides did not inhibit synaptic transmission. This inhibitory effect depended on the presynaptic activity and was affected by extracellular Ca2+ concentrations. The onset of the Mid peptide effect was shortened when the neuron was stimulated at a higher frequency, and the inhibition was more potent at 1 mM Ca2+ than at 5.1 mM Ca2+. These results suggest that the Doc2α -Munc13-1 interaction plays a role in a step before the final fusion step of synaptic vesicles with the presynaptic plasma membrane in the evoked neurotransmitter release process.
Proceedings of the National Academy of Sciences of the United States of America © 1998 National Academy of Sciences