Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion.
We have identified a novel 100 kDa coiled-coil protein, rabaptin-5, that specifically interacts with the GTP form of the small GTPase Rab5, a potent regulator of endocytic transport. It is mainly cytosolic, but a fraction colocalizes with Rab5 to early endosomes. Expression of a GTPase-deficient Rab5 mutant enhances the binding of rabaptin-5 to enlarged endosomes. Overexpression of rabaptin-5 alone is sufficient to promote expansion of early endosomes. Rab5 recruits rabaptin-5 to purified early endosomes in a GTP-dependent manner, demonstrating functional similarities with other members of the Ras superfamily. Immunodepletion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early endosome fusion. Rabaptin-5 is thus a Rab effector required for membrane docking and fusion.
European Molecular Biology Laboratory, Heidelberg Federal Republic of Germany.
H
H
Stenmark
G
G
Vitale
O
O
Ullrich
M
M
Zerial
D000595:Amino Acid Sequence; D001483:Base Sequence; D002474:Cell-Free System; D003600:Cytosol / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D015723:Gene Library; D005820:Genetic Testing; D007425:Intracellular Membranes / Q000737:chemistry / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D033921:Vesicular Transport Proteins; D015003:Yeasts / Q000502:physiology; D020696:rab5 GTP-Binding Proteins
D018076:DNA, Complementary; D005656:Fungal Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins