title: Rab11-FIP3 binds dynein light intermediate chain 2 and its overexpression fragments the Golgi complex.
abstract: The mechanochemical forces that move and position intracellular organelles and their intermediates in eukaryotic cells are provided by molecular motor proteins which include the cytoplasmic dynein-1 motor complex. Recently, we identified the Rab11 GTPase effector protein Rab11-FIP3 (henceforth, FIP3) as a novel binding-partner for dynein light intermediate chain 1 (DLIC-1, gene symbol DYNC1LI1), a subunit of cytoplasmic dynein-1. Here, we show that FIP3 also binds the dynein light intermediate chain 2 subunit (DLIC-2, gene symbol DYNC1LI2). We show that like DLIC-1, DLIC-2 binds the amino-terminal 435 amino acids of FIP3 and that FIP3 links Rab11a to DLIC-2. We also show that FIP3 recruits DLIC-2 onto membranes and that DLIC-2 is necessary for the accumulation of endocytosed-transferrin (Tfn) at the pericentrosomal endosomal-recycling compartment (ERC). Finally, we demonstrate that overexpression of FIP3 fragments the Golgi complex by sequestering cytoplasmic dynein-1. In conclusion, we have identified FIP3 as the first membrane-associated interacting-partner for DLIC-2 and propose that this interaction serves to control endosomal trafficking from sorting endosomes to the 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: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans
chemical_list: D002352:Carrier Proteins; C439063:RAB11FIP3 protein, human; C424131:DYNC1LI1 protein, human; D056445:Cytoplasmic Dyneins; C548808:DYNC1LI2 protein, human; D004398:Dyneins