Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6

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. Microvilli on epithelial cells can sense the surrounding fluid environment, but the regulatory mechanism behind their formation is mostly unknown. Here Miura et al. show that fluid shear stress serves as a trigger for microvilli formation via activation of the calcium ion channel TRPV6.