The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex.
Early endocytic membrane traffic is regulated by the small GTPase Rab5, which cycles between GTP- and GDP-bound states as well as between membrane and cytosol. The latter cycle depends on GDI, which functions as a Rab vehicle in the aqueous environment of the cytosol. Here, we report that formation of the GDI:Rab5 complex is stimulated by a cytosolic factor that we purified and then identified as p38 MAPK. We find that p38 regulates GDI in the cytosolic cycle of Rab5 and modulates endocytosis in vivo. Our observations reveal the existence of a cross-talk between endocytosis and the p38-dependent stress response, thus providing molecular evidence that endocytosis can be regulated by the environment.
Department of Biochemistry, Sciences II, University of Geneva, 30 quai Ernest Ansermet, 1211 4, Geneva, Switzerland.
V
V
Cavalli
F
F
Vilbois
M
M
Corti
M J
MJ
Marcote
K
K
Tamura
M
M
Karin
S
S
Arkinstall
J
J
Gruenberg
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins; D012694:Serine / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
D020730:Guanine Nucleotide Dissociation Inhibitors; D007093:Imidazoles; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D012694:Serine; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020696:rab5 GTP-Binding Proteins; C093642:SB 203580