title: KIF17 regulates RhoA-dependent actin remodeling at epithelial cell-cell adhesions.
abstract: The kinesin KIF17 localizes at microtubule plus-ends where it contributes to regulation of microtubule stabilization and epithelial polarization. We now show that KIF17 localizes at cell-cell adhesions and that KIF17 depletion inhibits accumulation of actin at the apical pole of cells grown in 3D organotypic cultures and alters the distribution of actin and E-cadherin in cells cultured in 2D on solid supports. Overexpression of full-length KIF17 constructs or truncation mutants containing the N-terminal motor domain resulted in accumulation of newly incorporated GFP-actin into junctional actin foci, cleared E-cadherin from cytoplasmic vesicles and stabilized cell-cell adhesions to challenge with calcium depletion. Expression of these KIF17 constructs also increased cellular levels of active RhoA, whereas active RhoA was diminished in KIF17-depleted cells. Inhibition of RhoA or its effector ROCK, or expression of LIMK1 kinase-dead or activated cofilin(S3A) inhibited KIF17-induced junctional actin accumulation. Interestingly, KIF17 activity toward actin depends on the motor domain but is independent of microtubule binding. Together, these data show that KIF17 can modify RhoA-GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells.
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Bipul R
authors.initials: BR
authors.lastname: Acharya
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Espenel
authors.affiliation: Gustave Roussy Institute, UMR-8126, 114 rue Edouard Vaillant, Villejuif 94805, France.
authors.forename: Fotine
authors.initials: F
authors.lastname: Libanje
authors.affiliation: Gustave Roussy Institute, UMR-8126, 114 rue Edouard Vaillant, Villejuif 94805, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Raingeaud
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Morgan
authors.affiliation: Gustave Roussy Institute, UMR-8126, 114 rue Edouard Vaillant, Villejuif 94805, France gek2006@med.cornell.edu fanny.jaulin@gustaveroussy.fr.
authors.forename: Fanny
authors.initials: F
authors.lastname: Jaulin
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY, USA gek2006@med.cornell.edu fanny.jaulin@gustaveroussy.fr.
authors.forename: Geri
authors.initials: G
authors.lastname: Kreitzer
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D016547:Kinesins / Q000502:physiology*; D054461:Lim Kinases / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C485813:KIF17 protein, human; C066737:RHOA protein, human; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054460:rho-Associated Kinases; D016547:Kinesins; D020742:rhoA GTP-Binding Protein
keywords: Actin; Cell–cell adhesion; Kinesin; Rho–GTPases