Action of brefeldin A blocked by activation of a pertussis-toxin-sensitive G protein

• Published in: Nature (London) 1992-03, Vol.356 (6367), p.344-346
• Main Authors: Ktistakis, Nicholas T, Linden, Maurine E, Roth, Michael G
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biology; Brefeldin A; Cell Compartmentation - drug effects; Cell Membrane Permeability; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; coat protein; Coatomer Protein; Cyclopentanes - antagonists & inhibitors; Fundamental and applied biological sciences. Psychology; Golgi apparatus; Golgi Apparatus - metabolism; GTP-Binding Proteins - metabolism; guanine nucleotide-binding protein; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Humanities and Social Sciences; In Vitro Techniques; inhibition; Intracellular Membranes - metabolism; letter; mastoparan; Membranes; Microtubule-Associated Proteins - metabolism; Molecular and cellular biology; multidisciplinary; Peptides; Pertussis Toxin; Protein Binding - drug effects; Proteins; reduction; release; Science; Science (multidisciplinary); Toxins; Virulence Factors, Bordetella - pharmacology; Wasp Venoms - pharmacology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/356344a0

IN many mammalian cells brefeldin A interferes with mechanisms that keep the Golgi apparatus separate from the endoplasmic reticulum 1–8 . The earliest effect of brefeldin A is release of the coat protein β -COP from the Golgi 9–11 . This release is blocked by pretreatment with GTP- γ S or AIF − 4 (ref. 12). The AIF − 4 ion activates heterotrimeric G proteins 13 but not proteins of the ras superfamily 14 , 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 15,16 , promotes binding of β -COP to Golgi membranes in vitro and antagonizes the effect of brefeldin A on β -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 G i /G O subfamily regulates association of coat components with Golgi membranes.