title: Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment.
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.
authors.affiliation: Molecular Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Horgan
authors.forename: Sara R
authors.initials: SR
authors.lastname: Hanscom
authors.forename: Rushee S
authors.initials: RS
authors.lastname: Jolly
authors.forename: Clare E
authors.initials: CE
authors.lastname: Futter
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology* / Q000648:ultrastructure; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D015415:Biomarkers; D056445:Cytoplasmic Dyneins; D051550:I-kappa B Kinase; D050505:Mutant Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C491731:IKBKG protein, human; C424131:DYNC1LI1 protein, human