Regulation of endosome fusion.
Homotypic fusion between early endosomes can be reconstituted in vitro. By using wortmannin and LY294002, inhibitors of phosphatidylinositol (Pl) 3-kinase, a requirement for this activity has been established in order for fusion to proceed efficiently. It has been shown that Pl 3-kinase activity is required downstream of rab5 activation, although a large excess of activated rab5 can overcome wortmannin inhibition. A series of experiments have also been performed which indicate a role for early endosomal autoantigen 1 (EEA1) in determining fusion efficiency. EEA1 dissociates from membranes following wortmannin treatment. It is proposed that the requirement of endosome fusion for Pl 3-kinase activity is to promote the association of EEA1 with endosomes.
Mills
I G
IG
Physiological Laboratory, University of Liverpool, UK.
Jones
A T
AT
Clague
M J
MJ
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D011992:Endosomes / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D052066:N-Ethylmaleimide-Sensitive Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D000077191:Wortmannin; D020696:rab5 GTP-Binding Proteins
D000730:Androstadienes; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D020696:rab5 GTP-Binding Proteins; D000077191:Wortmannin