Sun Jian, Wang Xiaolei, Li Chaocui, Mao Bingyu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650203, China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Biochem Biophys Res Commun. 2015 Jul 3;462(3):178-83. doi: 10.1016/j.bbrc.2015.04.065. Epub 2015 May 13.
Claudins are tetratransmembrane tight junction proteins and play important roles in regulating paracellular permeability of different nephron segments of the kidney. However, the roles of claudins in kidney development remain largely unknown. Here we studied the expression and functions of claudin-6 in Xenopus pronephros development. Xenopus claudin-6 is expressed in the developing pronephric tubule and duct but not glomus. Knockdown of claudin-6 by specific morpholino led to severe defects in pronephros tubular morphogenesis and blocked the terminal differentiation of the tubule cells. The claudin-6 morpholino targeted tubule cells showed failure of apical accumulation of actin and reduced lateral expression of tight junction protein Na/K-ATPase, suggesting an incomplete epithelization likely due to defected cell adhesions and apical-lateral polarity. Our work uncovered a novel role for claudin-6 in embryonic kidney development.
闭合蛋白是四跨膜紧密连接蛋白，在调节肾脏不同肾单位节段的细胞旁通透性方面发挥重要作用。然而，闭合蛋白在肾脏发育中的作用仍 largely 未知。在这里，我们研究了闭合蛋白 -6 在非洲爪蟾前肾发育中的表达和功能。非洲爪蟾闭合蛋白 -6 在发育中的前肾小管和导管中表达，但在肾小球中不表达。通过特异性吗啉代寡核苷酸敲低闭合蛋白 -6 导致前肾肾小管形态发生严重缺陷，并阻断了肾小管细胞的终末分化。靶向肾小管细胞的闭合蛋白 -6 吗啉代寡核苷酸显示肌动蛋白顶端积累失败，紧密连接蛋白 Na/K-ATP 酶的侧向表达减少，提示上皮化不完全可能是由于细胞黏附缺陷和顶端 - 侧向极性异常所致。我们的工作揭示了闭合蛋白 -6 在胚胎肾脏发育中的新作用。
