Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), México D.F. 07360, Mexico.
Department of Cell Biology, Center for Research and Advanced Studies (Cinvestav), México D.F. 07360, Mexico.
Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1714-1733. doi: 10.1016/j.bbamcr.2017.05.016. Epub 2017 May 26.
Silencing Zonula occludens 2 (ZO-2), a tight junctions (TJ) scaffold protein, in epithelial cells (MDCK ZO-2 KD) triggers: 1) Decreased cell to substratum attachment, accompanied by reduced expression of claudin-7 and integrin β1, and increased vinculin recruitment to focal adhesions and stress fibers formation; 2) Lowered cell-cell aggregation and appearance of wider intercellular spaces; 3) Increased RhoA/ROCK activity, mediated by GEF-HI recruitment to cell borders by cingulin; 4) Increased Cdc42 activity, mitotic spindle disorientation and the appearance of cysts with multiple lumens; 5) Increased Rac and cofilin activity, multiple lamellipodia formation and random cell migration but increased wound closure; 6) Diminished cingulin phosphorylation and disappearance of planar network of microtubules at the TJ region; and 7) Increased transepithelial electrical resistance at steady state, coupled to an increased expression of ZO-1 and claudin-4 and a decreased expression of claudin-2 and paracingulin. Hence, ZO-2 is a crucial regulator of Rho proteins activity and the development of epithelial cytoarchitecture and barrier function.
沉默紧密连接（TJ）支架蛋白闭锁小带蛋白 2（ZO-2）会在上皮细胞（MDCK ZO-2 KD）中引发：1）细胞与基底的附着减少，伴随 Claudin-7 和整合素 β1 的表达降低，以及黏着斑处 vinculin 的募集和应力纤维形成增加；2）细胞-细胞聚集减少，细胞间空间变宽；3）RhoA/ROCK 活性增加，由 cingulin 将 GEF-HI 募集到细胞边缘介导；4）Cdc42 活性增加，有丝分裂纺锤体错位，出现多个腔的小囊泡；5）Rac 和 cofilin 活性增加，形成多个片状伪足，细胞随机迁移但伤口愈合增加；6）cingulin 磷酸化减少，TJ 区微管平面网络消失；7）在稳定状态下，上皮细胞的跨上皮电阻增加，同时 ZO-1 和 Claudin-4 的表达增加，Claudin-2 和 paracingulin 的表达减少。因此，ZO-2 是 Rho 蛋白活性和上皮细胞形态发生和屏障功能发展的关键调节因子。
