TY - JOUR

T1 - Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis

AU - Schonteich, Eric

AU - Fielding, Andrew B.

AU - Matheson, Johanne

AU - Wilson, Gayle

AU - Yu, Xinzi

AU - Hickson, Gilles R X

AU - Srivastava, Sweta

AU - Baldwin, Stephen A

AU - Prekeris, Rytis

AU - Gould, Gwyn W

PY - 2005/10/5

Y1 - 2005/10/5

N2 - 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.

AB - 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.

KW - ADP-Ribosylation Factors

KW - Carrier Proteins

KW - Cell Line, Tumor

KW - Cell Membrane

KW - Cytokinesis

KW - Endocytosis

KW - Endosomes

KW - GTP Phosphohydrolases

KW - Humans

KW - I-kappa B Kinase

KW - Immunoprecipitation

KW - Models, Biological

KW - Multiprotein Complexes

KW - Protein Binding

KW - RNA Interference

KW - rab GTP-Binding Proteins

KW - Comparative Study

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1038/sj.emboj.7600803

DO - 10.1038/sj.emboj.7600803

M3 - Journal article

C2 - 16148947

VL - 24

SP - 3389

EP - 3399

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 19

ER -