title: Ena/VASP proteins can regulate distinct modes of actin organization at cadherin-adhesive contacts.
abstract: Functional interactions between classical cadherins and the actin cytoskeleton involve diverse actin activities, including filament nucleation, cross-linking, and bundling. In this report, we explored the capacity of Ena/VASP proteins to regulate the actin cytoskeleton at cadherin-adhesive contacts. We extended the observation that Ena/vasodilator-stimulated phosphoprotein (VASP) proteins localize at cell-cell contacts to demonstrate that E-cadherin homophilic ligation is sufficient to recruit Mena to adhesion sites. Ena/VASP activity was necessary both for F-actin accumulation and assembly at cell-cell contacts. Moreover, we identified two distinct pools of Mena within individual homophilic adhesions that cells made when they adhered to cadherin-coated substrata. These Mena pools localized with Arp2/3-driven cellular protrusions as well as at the tips of cadherin-based actin bundles. Importantly, Ena/VASP activity was necessary for both modes of actin activity to be expressed. Moreover, selective depletion of Ena/VASP proteins from the tips of cadherin-based bundles perturbed the bundles without affecting the protrusive F-actin pool. We propose that Ena/VASP proteins may serve as higher order regulators of the cytoskeleton at cadherin contacts through their ability to modulate distinct modes of actin organization at those contacts.
authors.affiliation: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors.forename: Jeanie A
authors.initials: JA
authors.lastname: Scott
authors.forename: Annette M
authors.initials: AM
authors.lastname: Shewan
authors.forename: Nicole R
authors.initials: NR
authors.lastname: den Elzen
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Loureiro
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D054460:rho-Associated Kinases
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; D047908:Intracellular Signaling Peptides and Proteins; D015638:Cytochalasin D; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases