Evidence of a role for heterotrimeric GTP-binding proteins in endosome fusion.
Guanosine triphosphate (GTP)-binding proteins are required for intracellular vesicular transport. Mastoparan is a peptide component of wasp venom that increases nucleotide exchange in some classes of G alpha subunits of regulatory heterotrimeric GTP-binding proteins (G proteins). Mastoparan and other compounds that increase nucleotide exchange by G proteins inhibited endosome fusion in vitro and reversed the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), a nonhydrolyzable GTP analog. Addition of beta gamma subunits of G proteins to the fusion assay antagonized the stimulatory effect of GTP-gamma-S, confirming the participation of G proteins. These results indicate that GTP-binding proteins are required for endosome fusion and in particular that a G protein is involved. Given the function of G proteins in signal transduction, these findings may provide insight into the mechanism by which endosomal vesicles become competent for fusion after their formation at the cell surface.
Colombo
M I
MI
Department of Cell Biology and Physiology, Washington University, School of Medicine, St. Louis, MO 63110.
Mayorga
L S
LS
Casey
P J
PJ
Stahl
P D
PD
D001692:Biological Transport; D004705:Endocytosis; D011992:Endosomes / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007425:Intracellular Membranes / Q000378:metabolism*; D046911:Macromolecular Substances; D008561:Membrane Fusion / Q000187:drug effects; D015388:Organelles / Q000502:physiology*; D010455:Peptides; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D010455:Peptides; D014862:Wasp Venoms; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins