RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1
RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1
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DOI：
10.1242/jcs.005306
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发表时间：
2007-06-01
影响因子：
4
通讯作者：
Brody, Steven L.
中科院分区：
文献类型：
--
作者：
Pan, Jiehong;You, Yingjian;Brody, Steven L.
直接细胞分化的程序依赖于Rho GTPases提供的严格的调控因子的时间表达。纤毛发生是一个复杂的过程，包括在顶端膜上的基底层的产生和对接，然后是纤毛轴突的产生。虽然纤毛蛋白质组已经被组装，但是指导纤毛细胞分化的程序还没有很好地建立起来，特别是在哺乳动物系统中。通过小鼠原代培养的气道上皮细胞，我们发现了纤毛发生的一个关键阶段，这一阶段需要肌动蛋白的顶端网状结构在时间上的建立，以便于基底体对接和随后的轴突生长。顶端网的形成和基体对接被肌动蛋白重塑的中断所阻止，并依赖于RhoA的激活。对foxj1缺失小鼠的分析为这一程序提供了额外的证据，foxj1缺失小鼠无法对接基底体，缺乏顶端肌动蛋白。Foxj1的表达与肌动蛋白网的形成一致，激活RhoA和RhoB，并且在RhoA抑制的情况下持续表达，表明Foxj1在纤毛发生过程中促进了RhoA。顶端ezrin定位也依赖于Foxj1、肌动蛋白重塑和RhoA，但对纤毛发生并不重要。因此，Foxj1和RhoA活性是哺乳动物纤毛发生过程中细胞骨架重塑的重要调控事件。
Programs that direct cellular differentiation are dependent on the strict temporal expression of regulatory factors that can be provided by Rho GTPases. Ciliogenesis is a complex sequence of events involving the generation and docking of basal bodies at the apical membrane, followed by ciliary axoneme generation. Although a cilia proteome has been assembled, programs that direct ciliated cell differentiation are not well established, particularly in mammalian systems. Using mouse primary culture airway epithelial cells, we identified a critical stage of ciliogenesis requiring the temporal establishment of an apical web-like structure of actin for basal body docking and subsequent axoneme growth. Apical web formation and basal body docking were prevented by interruption of actin remodeling and were dependent on RhoA activation. Additional evidence for this program was provided by analysis of Foxj1-null mice that failed to dock basal bodies and lacked apical actin. Foxj1 expression coincided with actin web formation, activated RhoA and RhoB, and persisted despite RhoA inhibition, suggesting that Foxj1 promoted RhoA during ciliogenesis. Apical ezrin localization was also dependent on Foxj1, actin remodeling, and RhoA, but was not critical for ciliogenesis. Thus, temporal Foxj1 and RhoA activity are essential regulatory events for cytoskeletal remodeling during mammalian ciliogenesis.