Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Biochemical and genetic approaches have identified a set of factors involved in microvilli formation; however, the underlying extrinsic regulatory mechanism of microvilli formation remains largely unknown. Here we demonstrate that fluid shear stress (FSS), an external mechanical cue, serves as a trigger for microvilli formation in human placental trophoblastic cells. We further reveal that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel plays a critical role in flow-induced Ca(2+) influx and microvilli formation. TRPV6 regulates phosphorylation of Ezrin via a Ca(2+)-dependent phosphorylation of Akt; this molecular event is necessary for microvillar localization of Ezrin in response to FSS. Our findings provide molecular insight into the microvilli-mediated mechanoresponsive cellular functions, such as epithelial absorption, signal perception and mechanotransduction.

中文翻译：

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流体剪切通过TRPV6的机械敏感性激活触发微绒毛的形成。

微绒毛是存在于分化的上皮细胞上的细胞膜突起，可以感知周围的液体环境并与周围的液体环境相互作用。生化和遗传方法已经确定了涉及微绒毛形成的一系列因素。然而，微绒毛形成的潜在外在调节机制仍是未知之数。在这里，我们证明流体剪切应力（FSS），一种外部机械提示，可作为人类胎盘滋养细胞中微绒毛形成的触发条件。我们进一步揭示，瞬态受体电位，香草类6型（TRPV6）钙离子通道在流量诱导的Ca（2+）流入和微绒毛形成中起关键作用。TRPV6通过Akt的Ca（2+）依赖磷酸化调节Ezrin的磷酸化；该分子事件对于响应FSS的Ezrin的微绒毛定位是必需的。我们的发现为微绒毛介导的机械反应性细胞功能（如上皮吸收，信号感知和机械转导）提供了分子洞察力。