title: Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in migrating fibroblasts.
abstract: Selectively stabilized microtubules (MTs) form in the lamella of fibroblasts and contribute to cell migration. A Rho-mDia-EB1 pathway regulates the formation of stable MTs, yet how selective stabilization of MTs is achieved is unknown. Kinesin activity has been implicated in selective MT stabilization and a number of kinesins regulate MT dynamics both in vitro and in cells. Here, we show that the mammalian homolog of Xenopus XKLP1, Kif4, is both necessary and sufficient for the induction of selective MT stabilization in fibroblasts. Kif4 localized to the ends of stable MTs and participated in the Rho-mDia-EB1 MT stabilization pathway since Kif4 depletion blocked mDia- and EB1-induced selective MT stabilization and EB1 was necessary for Kif4 induction of stable MTs. Kif4 and EB1 interacted in cell extracts, and binding studies revealed that the tail domain of Kif4 interacted directly with the N-terminal domain of EB1. Consistent with its role in regulating formation of stable MTs in interphase cells, Kif4 knockdown inhibited migration of cells into wounded monolayers. These data identify Kif4 as a novel factor in the Rho-mDia-EB1 MT stabilization pathway and cell migration.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Morris
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Guilherme P F
authors.initials: GP
authors.lastname: Nader
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Nagendran
authors.initials: N
authors.lastname: Ramalingam
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bartolini
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
mesh_terms: D000818:Animals; D002465:Cell Movement; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism*; D041681:NIH 3T3 Cells; D055550:Protein Stability; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C584107:EB1 protein, mouse; D008869:Microtubule-Associated Proteins; C089655:Kif4 protein, mouse; D016547:Kinesins; D020741:rho GTP-Binding Proteins