Abstract
Rab4 and Rab11 are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts specifically with the GTP-bound conformation of Rab4, and subsequent work has shown that it also interacts strongly with Rab11. We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested. It colocalizes with early endosomal markers including Rab4 and Rab11 as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment. Furthermore, expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family.
Highlights
Rab4 and Rab11 are small GTPases belonging to the Ras superfamily
Because of its interaction with two Rabs that function in endosomal recycling, its localization to the early endosomal recycling compartment, and its functional effects on the recycling process, we propose to name this the Rab coupling protein (RCP)
Rab proteins serve a critical role in the regulation of intracellular transport events
Summary
Rab and Rab are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts with the GTP-bound conformation of Rab, and subsequent work has shown that it interacts strongly with Rab. We have identified a novel 80-kDa protein that interacts with the GTP-bound conformation of Rab, and subsequent work has shown that it interacts strongly with Rab11 We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested It colocalizes with early endosomal markers including Rab and Rab as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment Expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. Rabphilin 11/ Rab11BP [25, 26], Rip11/pp75 [27], myosin Vb [28], and the Rab11-FIP family have been identified as interacting targets of Rab11 [29, 30]
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