Opposing roles of zyxin/LPP ACTA repeats and the LIM domain region in cell-cell adhesion.
Cadherins mediate cell-cell adhesion by linking cell junctions to actin networks. Although several actin regulatory systems have been implicated in cell-cell adhesion, it remains unclear how such systems drive cadherin-actin network formation and how they are regulated to coincide with initiation of adhesion. Previous work implicated VASP in assembly of cell-cell junctions in keratinocytes and the VASP-binding protein zyxin colocalizes with VASP at cell-cell junctions. Here we examine how domains in zyxin and its relative LPP contribute to cell-cell junction assembly. Using a quantitative assay for cell-cell adhesion, we demonstrate that zyxin and LPP function to increase the rate of early cell-cell junction assembly through the VASP-binding ActA repeat region. We also identify the LIM region of zyxin and LPP to be a regulatory domain that blocks function of these proteins. Deletion of the LIM domains drives adhesion and increases VASP level in detergent insoluble cadherin-actin. Dominant-negative zyxin/LPP mutants reduce the rate of adhesion, lower VASP levels in detergent-insoluble cadherin-actin networks, and allow for the accumulation of capping protein at cell-cell contacts. These data implicate the LIM domains of zyxin and LPP in regulating cell-cell junction assembly through VASP.
Hansen
Marc D H
MD
Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84102, USA. marchansen@byu.edu
Beckerle
Mary C
MC
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D004285:Dogs; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid
D015820:Cadherins; D011506:Proteins