Transient, phorbol ester-induced DOC2-Munc13 interactions in vivo.
Munc13-1 and DOC2 have been implicated in the regulation of exocytosis. Here we demonstrate in vivo that these two proteins undergo a transient phorbol ester-mediated and protein kinase C-independent interaction, resulting in the translocation of DOC2 from a vesicular localization to the plasma membrane. The translocation of DOC2 is dependent upon the DOC2 Munc interacting domain that binds specifically to Munc13-1, whereas the association of DOC2 with intracellular membranes is dependent on its C2 domains. This is the first direct in vivo demonstration of a protein-protein interaction between two presynaptic proteins and may represent a molecular basis for phorbol ester-dependent enhancement of exocytosis.
Duncan
R R
RR
Membrane Biology Group, Department of Biomedical Sciences, University of Edinburgh Medical School, Edinburgh EH8 9AG, United Kingdom.
Betz
A
A
Shipston
M J
MJ
Brose
N
N
Chow
R H
RH
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection
D000470:Alkaloids; D053119:Benzophenanthridines; D002135:Calcium-Binding Proteins; C091524:DOC2A protein, human; C490420:DOC2B protein, human; C490418:Doc2a protein, mouse; C490419:Doc2a protein, rat; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D010617:Phenanthridines; D011993:Recombinant Fusion Proteins; C485548:UNC13B protein, human; C103912:Unc13a protein, rat; C485549:Unc13b protein, mouse; D049452:Green Fluorescent Proteins; C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate