1. Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment.
- Author
-
Horgan CP, Hanscom SR, Jolly RS, Futter CE, and McCaffrey MW
- Subjects
- Animals, Biomarkers metabolism, Cell Line, Cell Membrane metabolism, Cell Membrane ultrastructure, Cell Polarity, Centrosome metabolism, Endosomes ultrastructure, Humans, I-kappa B Kinase chemistry, Mice, Microtubules metabolism, Microtubules ultrastructure, Models, Biological, Mutant Proteins metabolism, Protein Binding, Protein Structure, Tertiary, Protein Transport, RNA Interference, Cell Compartmentation, Cytoplasmic Dyneins metabolism, Endocytosis, Endosomes enzymology, I-kappa B Kinase metabolism, rab GTP-Binding Proteins metabolism
- Abstract
Several protein families control intracellular transport processes in eukaryotic cells. Here, we show that the Rab11 GTPase effector protein Rab11-FIP3 (henceforth, FIP3) directly interacts with the dynein light intermediate chain 1 (DLIC-1, gene symbol DYNC1LI1) subunit of the cytoplasmic dynein 1 motor protein complex. We show that Rab11a, FIP3 and DLIC-1 form a ternary complex and that DLIC-1 colocalises with endogenous FIP3 and Rab11a in A431 cells. We demonstrate that association between FIP3 and DLIC-1 at the cell periphery precedes minus-end-directed microtubule-based transport, that FIP3 recruits DLIC-1 onto membranes, and that knockdown of DLIC-1 inhibits pericentrosomal accumulation of key endosomal-recycling compartment (ERC) proteins. In addition, we demonstrate that expression of a DLIC-1-binding truncation mutant of FIP3 disrupts the ability of ERC proteins to accumulate pericentrosomally. On the basis of these and other data, we propose that FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport of material from peripheral sorting endosomes to the centrally located ERC.
- Published
- 2010
- Full Text
- View/download PDF