alpha-Actinin links LPP, but not zyxin, to cadherin-based junctions.
The actin regulator VASP localizes to cell-cell junctions and has been implicated in cell-cell adhesion. VASP is recruited to sites of actin dynamics by interactions with proline rich FPPPPP motifs. Zyxin and its relative LPP use FPPPPP motifs to recruit VASP to specific cellular locations, thus directing changes in actin dynamics. It has been proposed that zyxin and LPP localize to cell-cell junctions by binding alpha-actinin. However, the role of alpha-actinin in recruiting zyxin and LPP to cell-cell contacts has not been experimentally tested. Here we use zyxin and LPP fragments to demonstrate that the alpha-actinin binding site of both proteins independently targets to cell-cell junctions. While the alpha-actinin binding site is required for LPP localization and function at cell-cell contacts, zyxin localization and function at cell-cell contacts is independent of the alpha-actinin binding site. Perturbation of LPP function, but not that of zyxin, results in changes in anchoring of alpha-actinin to detergent-insoluble networks at cell-cell contacts.
Hansen
Marc D H
MD
Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, USA.
Beckerle
Mary C
MC
D000185:Actinin / Q000032:analysis / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D007365:Intercellular Junctions / Q000737:chemistry / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D000185:Actinin