Dynamics of epithelial cells and neurons through regulation of dephosphorylation and reactivation of cofilin

点击翻译按钮获取中文摘要

Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH). The human or mouse genome has three copies of Ssh genes (Ssh1-Ssh3). Previous in situ hybridization analyses revealed characteristic patterns of expression of each of the mouse ssh genes in both neuronal and non-neuronal tissues. Here we studied levels of endogenous expression of individual gene products and showed that expression of Ssh-2 and that of Ssh-3 are high in neural and epithelial tissues, respectively. To explore roles of Ssh-3 in epithelial tissues, we isolated derivatives of MDCK cells in which Ssh-3 can be knocked down upon addition of doxycycline. Because we detected Ssh-1 in MDCK cells, we further isolated sublines in which both Ssh-1 and Ssh-3 are knocked down and have been studying phenotypes of cell shape. To examine in vivo roles of Ssh-3 in epithelial morphogenesis, we generated Ssh-3-knock out mice. The Ssh-3-knock out mice are viable and fertile in two different backgrounds and we have been hunting for phenotypes of various epithelial tissues, such as mammary glands and kidney.