Role of the Polycystins as Mechanosensors of Extracellular Stiffness

Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00545.2020. Online ahead of print.ABSTRACTPolycystin-1 (PC-1) is a transmembrane protein, encoded by the PKD1 gene, mutated in Autosomal Dominant Polycystic Kidney Disease (ADPKD). This common genetic disorder, characterized by cyst formation in both kidneys, ultimately leading to renal failure, is still waiting for a definitive treatment. The overall function of PC-1 and the molecular mechanism responsible for cyst formation are slowly coming to light, but they are both still intensively studied. In particular, PC-1 has been proposed to act as a mechanosensor, although the precise signal that activates the mechanical properties of this protein has been long debated and questioned. In this Review we report studies and evidences of PC-1 function as a mechanosensor, starting from the peculiarity of its structure, through the long journey that progressively shed new light on the potential initiating events of cystogenesis, concluding with the description of PC-1 recently shown ability to sense the mechanical stimuli provided by the stiffness of the extracellular environment. These new findings have potentially important implications for the understanding of ADPKD pathophysiology and potentially for designing new therapies.PMID:33615892 | DOI:10.1152/ajprenal.00545.2020
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Source Type: research