Zyxin controls migration in epithelial-mesenchymal transition by mediating actin-membrane linkages at cell-cell junctions.
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.
Sperry
Rebecca Bakkevig
RB
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA.
Bishop
Nicholas H
NH
Bramwell
Jeremy J
JJ
Brodeur
Michael N
MN
Carter
Matthew J
MJ
Fowler
Brent T
BT
Lewis
Zachery B
ZB
Maxfield
Steve D
SD
Staley
Davis M
DM
Vellinga
Ryan M
RM
Hansen
Marc D H
MD
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
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D017228:Hepatocyte Growth Factor