title: Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis.
abstract: The dual Rab11/Arf binding proteins, family of Rab11-interacting proteins FIP3 and FIP4 function in the delivery of recycling endosomes to the cleavage furrow and are, together with Rab11, essential for completion of abscission, the terminal step of cytokinesis. Here, we report that both FIP3 and FIP4 bind Arf6 in a nucleotide-dependent manner but exhibit differential affinities for Rab11 and Arf6. Both FIP3 and FIP4 can form ternary complexes with Rab11 and Arf6. Arf6 is localised to the furrow and midbody and we show that Arf6-GTP functions to localise FIP3 and FIP4 to midbodies during cytokinesis. Exo70p, a component of the Exocyst complex, also localises to the furrow of dividing cells and interacts with Arf6. We show that depletion of Exo70p leads to cytokinesis failure and an impairment of FIP3 and Rab11 localisation to the furrow and midbody. Moreover, Exo70p co-immunoprecipitates FIP3 and FIP4. Hence, we propose that FIP3 and FIP4 serve to couple Rab11-positive vesicle traffic from recycling endosomes to the cleavage furrow/midbody where they are tethered prior to fusion events via interactions with Arf6 and the Exocyst.
authors.affiliation: Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Fielding
authors.forename: Eric
authors.initials: E
authors.lastname: Schonteich
authors.forename: Johanne
authors.initials: J
authors.lastname: Matheson
authors.forename: Gayle
authors.initials: G
authors.lastname: Wilson
authors.forename: Xinzi
authors.initials: X
authors.lastname: Yu
authors.forename: Gilles R X
authors.initials: GR
authors.lastname: Hickson
authors.forename: Sweta
authors.initials: S
authors.lastname: Srivastava
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Baldwin
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
authors.forename: Gwyn W
authors.initials: GW
authors.lastname: Gould
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D047468:Immunoprecipitation; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D002352:Carrier Proteins; D020558:GTP Phosphohydrolases; D051550:I-kappa B Kinase; D046912:Multiprotein Complexes; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C491731:IKBKG protein, human; C439063:RAB11FIP3 protein, human; C000715348:ARF6 protein, human