Piezo mechanosensory channels regulate centrosome integrity and mitotic entry
Date of Original Version
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 Ca2+ 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) Ca2+-sensitive reporter, we show that perturbations in Piezo modulate Ca2+ 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 Ca2+ within a defined range, possibly through sensing cell intrinsic forces from microtubules.
Publication Title, e.g., Journal
Proceedings of the National Academy of Sciences of the United States of America
David, Liron, Laurel Martinez, Qiongchao Xi, Kameron A. Kooshesh, Ying Zhang, Jagesh V. Shah, Richard L. Maas, and Hao Wu. "Piezo mechanosensory channels regulate centrosome integrity and mitotic entry." Proceedings of the National Academy of Sciences of the United States of America 120, 1 (2023). doi: 10.1073/pnas.2213846120.