Abstract
Nuclei of cells respond to local mechanical cues with changes in their size, morphology, and motility, to maintain tissue homeostasis and proper functions. Previous studies indicated that the external forces are coupled to nuclei through the surrounding cytoskeleton network linked to the nuclear envelope, but the molecules that directly interact with outside environments are unclear. Here we show that the fluid shear stress applied to MDCK cells caused the nucleus to shrink through a Ca2+ dependent signaling pathway. Inhibiting Ca2+ permeable mechanosensitive Piezo1 channels, with the specific inhibitor GsMTx4, eliminated the nuclear changes. Piezo1 knockdown with miRNA that targets Piezo1 significantly reduced the nuclear shrinkage under shear stress. Activation of Piezo1 with Yoda1 caused similar nucleus shrinkage without shear stress. These results demonstrate that Piezo1 channel is accountable for transmitting the shear force input to nuclei via Ca2+ signaling. To assess the relative contributions of Ca2+ and cytoskeleton reorganization on force transduction, we examined F-actin reorganization under shear stress and static conditions, and showed that reorganization is not necessary for the nucleus shrinkage. These results emphasize the role of the mechanosensitive channels as primary transducers in force transmission to the nucleus.
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