title: Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration.
abstract: Cell migration is a highly dynamic process that plays pivotal roles in both physiological and pathological processes. We have previously reported that p130Cas supports cell migration through the binding to Src as well as phosphorylation-dependent association with actin retrograde flow at focal adhesions. However, it remains elusive how phosphorylated Cas interacts with actin cytoskeletons. We observe that the actin-binding protein, tensin 1, co-localizes with Cas, but not with its phosphorylation-defective mutant, at focal adhesions in leading regions of migrating cells. While a truncation mutant of tensin 1 that lacks the phosphotyrosine-binding PTB and SH2 domains (tensin 1-SH2PTB) poorly co-localizes or co-immunoprecitates with Cas, bacterially expressed recombinant tensin 1-SH2PTB protein binds to Casin vitroin a Cas phosphorylation-dependent manner. Furthermore, exogenous expression of tensin 1-SH2PTB, which is devoid of the actin-interacting motifs, interferes with the Cas-driven cell migration, slows down the inward flux of Cas molecules, and impedes the displacement of Cas molecules from focal adhesions. Taken together, our results show that tensin 1 links inwardly moving actin cytoskeletons to phosphorylated Cas at focal adhesions, thereby driving cell migration.
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Singapore.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, Block EA, #03-12, 117575, Singapore.
authors.forename: Song Hui
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Machiyama
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawauchi
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Keigo
authors.initials: K
authors.lastname: Araki
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Singapore Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, Block EA, #03-12, 117575, Singapore Department of Rehabilitation for the Movement Functions, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan Laboratory for Mechanical Medicine, Locomotive Syndrome Research Institute, Nadogaya Hospital, 687-4 Nadogaya, Kashiwa, Chiba 277-0032, Japan ys454-ind@umin.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
keywords: Actin cytoskeleton; Cell migration; Focal adhesion; P130Cas; Tensin 1