Divergent function of polycystin 1 and polycystin 2 in cell size regulation

Biochem Biophys Res Commun. 2020 Jan 8;521(2):290-295. doi: 10.1016/j.bbrc.2019.10.074. Epub 2019 Oct 24.


Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, the genes encoding polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC1 and PC2 localize to the primary cilium and form a protein complex, which is thought to regulate signaling events. PKD1 mutations are associated with a stronger phenotype than PKD2, suggesting the existence of PC1 specific functions in renal tubular cells. However, the evidence for diverging molecular functions is scant. The bending of cilia by fluid flow induces a reduction in cell size through a mechanism that involves the kinase LKB1 but not PC2. Here, using different in vitro approaches, we show that contrary to PC2, PC1 regulates cell size under flow and thus phenocopies the loss of cilia. PC1 is required to couple mechanical deflection of cilia to mTOR in tubular cells. This study pinpoints divergent functions of the polycystins in renal tubular cells that may be relevant to disease severity in ADPKD.

Keywords: ADPKD; Cilia; Flow; Polycystins; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Cell Size / drug effects*
  • Cells, Cultured
  • Cilia / metabolism
  • Humans
  • Kidney Tubules / cytology
  • Mutation
  • Polycystic Kidney, Autosomal Dominant / pathology*
  • TOR Serine-Threonine Kinases
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / physiology*


  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • TOR Serine-Threonine Kinases