Action of brefeldin A blocked by activation of a pertussis-toxin-sensitive G protein.
In many mammalian cells brefeldin A interferes with mechanisms that keep the Golgi appartus separate from the endoplasmic reticulum. The earliest effect of brefeldin A is release of the coat protein beta-COP from the Golgi. This release is blocked by pretreatment with GTP-gamma S or AlF4- (ref. 12). The AlF4- ion activates heterotrimeric G proteins but not proteins of the ras superfamily, suggesting that a heterotrimeric G protein might control membrane transfer from the endoplasmic reticulum to the Golgi. We report here that mastoparan, a peptide that activates heterotrimeric G proteins, promotes binding of beta-COP to Golgi membranes in vitro and antagonizes the effect of brefeldin A on beta-COP in perforated cells and on isolated Golgi membranes. This inhibition is greatly diminished if cells are pretreated with pertussis toxin before perforation. Thus, a heterotrimeric G protein of the Gi/Go subfamily regulates association of coat components with Golgi membranes.
Ktistakis
N T
NT
Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas 75235-9038.
Linder
M E
ME
Roth
M G
MG
D020126:Brefeldin A; D002451:Cell Compartmentation / Q000187:drug effects; D002463:Cell Membrane Permeability; D020756:Coatomer Protein; D003517:Cyclopentanes / Q000037:antagonists & inhibitors*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010455:Peptides; D037342:Pertussis Toxin; D011485:Protein Binding / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014862:Wasp Venoms / Q000494:pharmacology
D020756:Coatomer Protein; D003517:Cyclopentanes; D036341:Intercellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D010455:Peptides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D020126:Brefeldin A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins