Abstract
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 Ca2+ influx and microvilli formation. TRPV6 regulates phosphorylation of Ezrin via a Ca2+-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.
Highlights
Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment
We fabricate a multilayer microfluidic device to analyse material transport through the cells and to observe cellular responses to a broad range of fluid shear stress (FSS) (Fig. 1b,c). We show that both BeWo trophoblastic cells and villous trophoblasts form abundant microvilli of varying lengths depending on the flow rate, whereas the cells under static fluid conditions have sparse microvilli
We demonstrate that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel is essential in FSS-induced Ca2 þ influx and microvilli formation in
Summary
Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Microvilli provide greater surface area on the apical side of cells and enable asymmetric localization of membrane transporters, cytoskeletal proteins and enzymes for polarized cellular function[3] Various cell types, such as cells of the intestinal epithelia, proximal tubule of the kidney, nasal epithelia and placental syncytium[4], form microvillar surfaces that effectively sense and interact with the fluid environment. We fabricate a multilayer microfluidic device to analyse material transport through the cells and to observe cellular responses to a broad range of FSS (Fig. 1b,c) Using this device, we show that both BeWo trophoblastic cells and villous trophoblasts form abundant microvilli of varying lengths depending on the flow rate, whereas the cells under static fluid conditions have sparse microvilli. We demonstrate that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel is essential in FSS-induced Ca2 þ influx and microvilli formation in
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