Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain.

Rab11-FIP2 is a recently described member of the Rip11/Rab11-FIP/Rab coupling protein family of Rab11 interacting proteins. Rab11-FIP2 interacts with both Rab11 and myosin Vb and co-localizes with Rab11 in both HeLa and Madin-Darby canine kidney cells (Hales, C. M., Griner, R., Hobdy-Henderson, K. C., Dorn, M. C., Hardy, D., Kumar, ...
R., Navarre, J., Chan, E. K., Lapierre, L. A., and Goldenring, J. R. (2001) J. Biol. Chem. 276, 39067-390751). Here, we characterized the specificity of the interaction between Rab11-FIP2 and Rab11 and report that it does not interact with Rab4, Rab3, Rab5, Rab6, or Rab7. We demonstrate that the COOH-terminal region of Rab11-FIP2, which contains the Rab11 binding domain (RBD), is necessary and sufficient for its early endosomal membrane association. In contrast, the amino-terminal region, which contains a phospholipid binding C2-domain, by itself was insufficient for membrane binding. Expression of a deletion mutant of Rab11-FIP2, containing the RBD, caused tubulation of a transferrin receptor-positive early endosomal compartment in HeLa cells. Endogenous Rab11 was also associated with this compartment. This phenotype cannot be reversed by excess wild-type Rab11, or dominant-positive Rab11 (Rab11Q70L), suggesting that Rab11-FIP2 functions downstream of Rab11 in endosomal trafficking.
Mesh Terms:
Amino Acid Sequence, Biological Transport, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Endosomes, Green Fluorescent Proteins, Hela Cells, Humans, Intracellular Membranes, Luminescent Proteins, Membrane Proteins, Microscopy, Fluorescence, Molecular Sequence Data, Phenotype, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins, Transfection, Transferrin, Two-Hybrid System Techniques, rab GTP-Binding Proteins
J. Biol. Chem.
Date: Jul. 26, 2002
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