Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Veronique Chauvet, Xin Tian, Herve Husson, David H. Grimm, Tong Wang, Thomas Hieseberger, Peter Igarashi, Anton M. Bennett, Oxana Ibraghimov-Beskrovnaya, Stefan Somlo, Michael J. Caplan
Veronique Chauvet, Xin Tian, Herve Husson, David H. Grimm, Tong Wang, Thomas Hieseberger, Peter Igarashi, Anton M. Bennett, Oxana Ibraghimov-Beskrovnaya, Stefan Somlo, Michael J. Caplan
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Article Nephrology

Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus

Abstract

Polycystin-1, which is encoded by a gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), is involved in cell-matrix interactions as well as in ciliary signaling. The precise mechanisms by which it functions, however, remain unclear. Here we find that polycystin-1 undergoes a proteolytic cleavage that releases its C-terminal tail (CTT), which enters the nucleus and initiates signaling processes. The cleavage occurs in vivo in association with alterations in mechanical stimuli. Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus.

Authors

Veronique Chauvet, Xin Tian, Herve Husson, David H. Grimm, Tong Wang, Thomas Hieseberger, Peter Igarashi, Anton M. Bennett, Oxana Ibraghimov-Beskrovnaya, Stefan Somlo, Michael J. Caplan

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Mutations that prevent the assembly of cilia are associated with nuclear...
Mutations that prevent the assembly of cilia are associated with nuclear accumulation of the CTT. Kidneys from KIF3A KO mice (Kif3A–/–) (A–F) and WT mice (Kif3A+/+) (G–I) were examined by immunofluorescence microscopy using Mex-46–AP (A and G) or preimmune serum (preI) (D). Nuclei are stained with Hoechst 33342 (B, E, and H), and superposition of Mex-46–AP (red) and Hochst (blue) staining is depicted in C, F, and I. In sections prepared from KIF3A KO animals, nuclei (arrows) of cyst epithelial cells, as well as the epithelial cells lining neighboring tubules, are stained with Mex-46–AP (A) but not with preimmune serum (D). No nuclear staining with Mex-46–AP is detected in tubule cells of WT mice (G).