Piezo mechanosensory channels regulate centrosome integrity and mitotic entry

Abstract

Piezo1 and 2 are evolutionarily conserved mechanosensory cation channels known to function on the cell surface by responding to external pressure and transducing a mechanically activated Ca 2+ current. Here we show that both Piezo1 and 2 also exhibit concentrated intracellular localization at centrosomes. Both Piezo1 and 2 loss-of-function and Piezo1 activation by the small molecule Yoda1 result in supernumerary centrosomes, premature centriole disengagement, multi-polar spindles, and mitotic delay. By using a GFP, Calmodulin and M13 Protein fusion (GCaMP) Ca 2+ -sensitive reporter, we show that perturbations in Piezo modulate Ca 2+ flux at centrosomes. Moreover, the inhibition of Polo-like-kinase 1 eliminates Yoda1-induced centriole disengagement. Because previous studies have implicated force generation by microtubules as essential for maintaining centrosomal integrity, we propose that mechanotransduction by Piezo maintains pericentrosomal Ca 2+ within a defined range, possibly through sensing cell intrinsic forces from microtubules.