Polycystin-1 Regulates Actomyosin Contraction and the Cellular Response to Extracellular Stiffness

Elisa Agnese Nigro, Gianfranco Distefano, Marco Chiaravalli, Vittoria Matafora, Maddalena Castelli, Angela Pesenti Gritti, Angela Bachi, Alessandra Boletta

Research output: Contribution to journalArticlepeer-review


Polycystin-1 (PC-1) and 2 (PC-2) are the products of the PKD1 and PKD2 genes, which are mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). They form a receptor/channel complex that has been suggested to function as a mechanosensor, possibly activated by ciliary bending in the renal tubule, and resulting in calcium influx. This model has recently been challenged, leaving the question as to which mechanical stimuli activate the polycystins still open. Here, we used a SILAC/Mass-Spec approach to identify intracellular binding partners of tagged-endogenous PC-1 whereby we detected a class of interactors mediating regulation of cellular actomyosin contraction. Accordingly, using gain and loss-of-function cellular systems we found that PC-1 negatively regulates cellular contraction and YAP activation in response to extracellular stiffness. Thus, PC-1 enables cells to sense the rigidity of the extracellular milieu and to respond appropriately. Of note, in an orthologous murine model of PKD we found evidence of increased actomyosin contraction, leading to enhanced YAP nuclear translocation and transcriptional activity. Finally, we show that inhibition of ROCK-dependent actomyosin contraction by Fasudil reversed YAP activation and significantly improved disease progression, in line with recent studies. Our data suggest a possible direct role of PC-1 as a mechanosensor of extracellular stiffness.

Original languageEnglish
Article number16640
JournalScientific Reports
Issue number1
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Polycystin-1 Regulates Actomyosin Contraction and the Cellular Response to Extracellular Stiffness'. Together they form a unique fingerprint.

Cite this