RRC ID 51920
Author Nishimura T, Ito S, Saito H, Hiver S, Shigetomi K, Ikenouchi J, Takeichi M.
Title DAAM1 stabilizes epithelial junctions by restraining WAVE complex-dependent lateral membrane motility.
Journal J Cell Biol
Abstract Epithelial junctions comprise two subdomains, the apical junctional complex (AJC) and the adjacent lateral membrane contacts (LCs), that span the majority of the junction. The AJC is lined with circumferential actin cables, whereas the LCs are associated with less-organized actin filaments whose roles are elusive. We found that DAAM1, a formin family actin regulator, accumulated at the LCs, and its depletion caused dispersion of actin filaments at these sites while hardly affecting circumferential actin cables. DAAM1 loss enhanced the motility of LC-forming membranes, leading to their invasion of neighboring cell layers, as well as disruption of polarized epithelial layers. We found that components of the WAVE complex and its downstream targets were required for the elevation of LC motility caused by DAAM1 loss. These findings suggest that the LC membranes are motile by nature because of the WAVE complex, but DAAM1-mediated actin regulation normally restrains this motility, thereby stabilizing epithelial architecture, and that DAAM1 loss evokes invasive abilities of epithelial cells.
Volume 215(4)
Pages 559-573
Published 2016-11-21
DOI 10.1083/jcb.201603107
PII jcb.201603107
PMID 27807130
PMC PMC5119936
MeSH Actin-Related Protein 2-3 Complex / metabolism Actins / metabolism Animals Cadherins / metabolism Cell Membrane / metabolism* Cell Surface Extensions / metabolism Epithelial Cells / metabolism* HEK293 Cells Humans Intercellular Junctions / metabolism* Mice Microfilament Proteins / metabolism* Multiprotein Complexes / metabolism* Signal Transduction alpha Catenin / metabolism beta Catenin / metabolism rac GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / metabolism*
IF 8.811
Times Cited 10
Resource
Human and Animal Cells 293T(RCB2202)