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.
Department of Cell Biology and Physiology, Washington University, School of Medicine, St. Louis, MO 63110.
M I
MI
Colombo
L S
LS
Mayorga
P J
PJ
Casey
P D
PD
Stahl
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