| First Author | David L | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 1 | Pages | e2213846120 |
| PubMed ID | 36574677 | Mgi Jnum | J:348695 |
| Mgi Id | MGI:7495440 | Doi | 10.1073/pnas.2213846120 |
| Citation | David L, et al. (2023) Piezo mechanosensory channels regulate centrosome integrity and mitotic entry. Proc Natl Acad Sci U S A 120(1):e2213846120 |
| abstractText | 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. |
