DAAM1 stabilizes epithelial junctions by restraining WAVE complex-dependent lateral membrane motility.
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.
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan tnishimura@cdb.riken.jp takeichi@cdb.riken.jp.
Tamako
T
Nishimura
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
Shoko
S
Ito
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
Hiroko
H
Saito
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
Sylvain
S
Hiver
Department of Biology, Faculty of Sciences, Kyushu University, Nishi-Ku, Fukuoka 819-0395, Japan.
Kenta
K
Shigetomi
Department of Biology, Faculty of Sciences, Kyushu University, Nishi-Ku, Fukuoka 819-0395, Japan.
Junichi
http://orcid.org/0000-0002-2936-3548
J
Ikenouchi
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan tnishimura@cdb.riken.jp takeichi@cdb.riken.jp.
Masatoshi
http://orcid.org/0000-0002-9931-3378
M
Takeichi
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D015820:Cadherins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D051178:alpha Catenin; D051176:beta Catenin; C500365:Daam1 protein, mouse; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins