TIP47 is a key effector for Rab9 localization.
The human genome encodes approximately 70 Rab GTPases that localize to the surfaces of distinct membrane compartments. To investigate the mechanism of Rab localization, chimeras containing heterologous Rab hypervariable domains were generated, and their ability to bind seven Rab effectors was quantified. Two chimeras could bind effectors for two distinctly localized Rabs; a Rab5/9 hybrid bound both Rab5 and Rab9 effectors, and a Rab1/9 hybrid bound to certain Rab1 and Rab9 effectors. These unusual chimeras permitted a test of the importance of effector binding for Rab localization. In both cases, changing the cellular concentration of a key Rab9 effector, which is called tail-interacting protein of 47 kD, moved a fraction of the proteins from their parental Rab localization to that of Rab9. Thus, relative concentrations of certain competing effectors could determine a chimera's localization. These data confirm the importance of effector interactions for Rab9 localization, and support a model in which effector proteins rely on Rabs as much as Rabs rely on effectors to achieve their correct steady state localizations.
Aivazian
Dikran
D
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Serrano
Ramon L
RL
Pfeffer
Suzanne
S
D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000032:analysis; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; D011257:Pregnancy Proteins; C097227:RABEP1 protein, human; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; C079856:RAB9A protein, human; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins