Warner Stephen J, Longmore Gregory D
Department of Medicine, Washington University, St. Louis, MO 63110, USA.
J Cell Biol. 2009 Jun 15;185(6):1111-25. doi: 10.1083/jcb.200901029. Epub 2009 Jun 8.
Maintenance and remodeling of adherens junctions (AJs) and cell shape in epithelia are necessary for the development of functional epithelia and are commonly altered during cancer progression/metastasis. Although formation of nascent AJs has received much attention, whether shared mechanisms are responsible for the maintenance and remodeling of AJs in dynamic epithelia, particularly in vivo, is not clear. Using clonal analysis in the postmitotic Drosophila melanogaster pupal eye epithelium, we demonstrate that Rho1 is required to maintain AJ integrity independent of its role in sustaining apical cell tension. Rho1 depletion in a remodeling postmitotic epithelium disrupts AJs but only when depleted in adjacent cells. Surprisingly, neither of the Rho effectors, Rok or Dia, is necessary downstream of Rho1 to maintain AJs; instead, Rho1 maintains AJs by inhibiting Drosophila epithelial cadherin endocytosis in a Cdc42/Par6-dependent manner. In contrast, depletion of Rho1 in single cells decreases apical tension, and Rok and myosin are necessary, while Dia function also contributes, downstream of Rho1 to sustain apical cell tension.
在上皮细胞中,黏着连接(AJs)的维持和重塑以及细胞形态对于功能性上皮细胞的发育是必需的,并且在癌症进展/转移过程中通常会发生改变。尽管新生AJs的形成受到了很多关注,但尚不清楚是否存在共同机制负责动态上皮细胞中AJs的维持和重塑,尤其是在体内。通过在有丝分裂后果蝇蛹眼上皮细胞中进行克隆分析,我们证明Rho1对于维持AJ完整性是必需的,这与其在维持顶端细胞张力中的作用无关。在重塑的有丝分裂后上皮细胞中Rho1缺失会破坏AJs,但仅在相邻细胞中缺失时才会发生。令人惊讶的是,Rho的效应器Rok或Dia在Rho1下游对于维持AJs并非必需;相反,Rho1通过以Cdc42/Par6依赖的方式抑制果蝇上皮钙黏蛋白的内吞作用来维持AJs。相比之下,单细胞中Rho1的缺失会降低顶端张力,Rok和肌球蛋白是必需的,而Dia的功能在Rho1下游也有助于维持顶端细胞张力。