title: Zyxin controls migration in epithelial-mesenchymal transition by mediating actin-membrane linkages at cell-cell junctions.
abstract: Development is punctuated by morphogenetic rearrangements of epithelial tissues, including detachment of motile cells during epithelial-mesenchymal transition (EMT). Dramatic actin rearrangements occur as cell-cell junctions are dismantled and cells become independently motile during EMT. Characterizing dynamic actin rearrangements and identifying actin machinery driving these rearrangements is essential for understanding basic mechanisms of cell-cell junction remodeling. Using immunofluorescence and live cell imaging of scattering MDCK cells we examine dynamic actin rearrangement events during EMT and demonstrate that zyxin-VASP complexes mediate linkage of dynamic medial actin networks to adherens junction (AJ) membranes. A functional analysis of zyxin in EMT reveals its role in regulating disruption of actin membrane linkages at cell-cell junctions, altering cells' ability to fully detach and migrate independently during EMT. Expression of a constitutively active zyxin mutant results in persistent actin-membrane linkages and cell migration without loss of cell-cell adhesion. We propose zyxin functions in morphogenetic rearrangements, maintaining collective migration by transducing individual cells' movements through AJs, thus preventing the dissociation of individual migratory cells.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA.
authors.forename: Rebecca Bakkevig
authors.initials: RB
authors.lastname: Sperry
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Bishop
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Bramwell
authors.forename: Michael N
authors.initials: MN
authors.lastname: Brodeur
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Carter
authors.forename: Brent T
authors.initials: BT
authors.lastname: Fowler
authors.forename: Zachery B
authors.initials: ZB
authors.lastname: Lewis
authors.forename: Steve D
authors.initials: SD
authors.lastname: Maxfield
authors.forename: Davis M
authors.initials: DM
authors.lastname: Staley
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Vellinga
authors.forename: Marc D H
authors.initials: MD
authors.lastname: Hansen
mesh_terms: D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D048430:Cell Shape; D054338:Cell Transdifferentiation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D017228:Hepatocyte Growth Factor