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PubMed · 16769818

TIP47 is a key effector for Rab9 localization.

Dikran Aivazian·Ramon L Serrano·Suzanne Pfeffer
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Abstract

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.

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Binding, CompetitiveDNA-Binding ProteinsEndosomesGreen Fluorescent ProteinsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsModels, BiologicalPerilipin-3Pregnancy ProteinsProtein Structure, TertiaryRecombinant Fusion ProteinsVesicular Transport Proteinsrab GTP-Binding Proteinsrab1 GTP-Binding Proteinsrab5 GTP-Binding ProteinsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Dikran Aivazian, Ramon L Serrano, Suzanne Pfeffer. 2006-06-12. TIP47 is a key effector for Rab9 localization.. https://doi.org/10.1083/jcb.200510010

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