Ngok Siu P, Anastasiadis Panos Z
Department of Cancer Biology; Mayo Clinic Comprehensive Cancer Center; Jacksonville, FL, USA.
Tissue Barriers. 2013 Dec 1;1(5):e27132. doi: 10.4161/tisb.27132. Epub 2013 Nov 15.
Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.
Rho GTP酶是调节细胞骨架的蛋白质，介导细胞间连接的形成。Rho鸟嘌呤核苷酸交换因子（Rho GEFs）对其进行局部激活以及下游效应器的选择性激活，已成为细胞黏附领域的活跃研究方向。我们最近报道，Rho特异性GEFs Syx（结合Synectin的RhoA交换因子）和TEM4（肿瘤内皮标志物4）对于内皮细胞连接成熟和屏障功能均至关重要。Syx通过其C末端PDZ结合基序被招募至细胞接触部位，并与Mupp1和Crumb极性复合体相互作用，而TEM4的连接定位则需要其N末端结构域以及与钙黏蛋白-连环蛋白复合体的相互作用。我们的研究结果支持RhoA在连接形成和维持中的多种作用。它们还表明，RhoA激活与Dia1和/或ROCK信号的选择性偶联对于确定内皮细胞连接完整性至关重要。
