Direct interaction between the ARF-specific guanine nucleotide exchange factor msec7-1 and presynaptic Munc13-1.
Msec7-1, a mammalian homologue of yeast sec7p, is a specific GDP/GTP exchange factor for small G-proteins of the ARF family. Overexpression of msec7-1 in Xenopus neuromuscular junctions leads to an increase in synaptic transmitter release that is most likely caused by an increase in the pool of readily releasable vesicles. However, the molecular mechanisms by which msec7-1 is targeted to presynaptic compartments and enhances neurotransmitter release are not known. In the present study, we demonstrate that msec7-1 interacts directly with Munc13-1, a phorbol ester-dependent enhancer of neurotransmitter release that is specifically localized to presynaptic transmitter release zones. Given that Munc13-1 and msec7-1 participate in very similar presynaptic processes and because Munc13-1 is specifically targeted to presynaptic active zones, we suggest that the msec7-1/Munc13-1 interaction serves to colocalize the two proteins at the active zone, a subcellular compartment with extremely high membrane turnover.
Neeb
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Max-Planck-Institut für experimentelle Medizin, Abteilung Molekulare Neurobiologie, Göttingen, Germany.
Koch
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H
Schürmann
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Brose
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D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D002846:Chromatography, Affinity; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D001616:beta-Galactosidase / Q000378:metabolism
D001426:Bacterial Proteins; C491661:Cyth 1 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011506:Proteins; C066755:Sec7 guanine nucleotide exchange factors; C103912:Unc13a protein, rat; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D020727:ADP-Ribosylation Factors