Zonula occludens 2 regulates Rho proteins activity and the development of epithelial cytoarchitecture and barrier function.
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 b1, 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.
Biochimica et biophysica acta. Molecular cell research