Nishimura Tamako, Ito Shoko, Saito Hiroko, Hiver Sylvain, Shigetomi Kenta, Ikenouchi Junichi, Takeichi Masatoshi
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan
RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
J Cell Biol. 2016 Nov 21;215(4):559-573. doi: 10.1083/jcb.201603107. Epub 2016 Nov 2.
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.
上皮连接由两个亚结构域组成，即顶端连接复合体（AJC）和相邻的侧膜接触（LCs），它们跨越了连接的大部分区域。AJC内衬有周向肌动蛋白束，而LCs与组织较松散的肌动蛋白丝相关，其作用尚不清楚。我们发现，一种formin家族肌动蛋白调节剂DAAM1在LCs处积累，其缺失导致这些位点的肌动蛋白丝分散，而对周向肌动蛋白束几乎没有影响。DAAM1的缺失增强了形成LC的膜的运动性，导致它们侵入相邻细胞层，以及破坏极化上皮层。我们发现，WAVE复合体的成分及其下游靶点是DAAM1缺失导致LC运动性升高所必需的。这些发现表明，由于WAVE复合体的存在，LC膜本质上是可运动的，但DAAM1介导的肌动蛋白调节通常会抑制这种运动性，从而稳定上皮结构，并且DAAM1的缺失会引发上皮细胞的侵袭能力。
