Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Veronique Chauvet, … , Stefan Somlo, Michael J. Caplan
Veronique Chauvet, … , Stefan Somlo, Michael J. Caplan
Published November 15, 2004
Citation Information: J Clin Invest. 2004;114(10):1433-1443. https://doi.org/10.1172/JCI21753.
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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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Figure 1

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The CTT of polycystin-1 is detected in the nuclei of renal tubular epith...
The CTT of polycystin-1 is detected in the nuclei of renal tubular epithelial cells in transgenic mice. (A–I) Kidneys from mice overexpressing murine polycystin-1 (Tg) (D–I) and kidneys from WT littermates (A–C) were processed for immunofluorescence using an antibody (Mex-46) specific for the CTT of polycystin-1 (pc-1) (A–F) or with the corresponding preimmune serum (G–I). Nuclei are visualized by staining with Hoechst 33342 (B, E, and H), and superposition of antibody (red) and nuclear (blue) staining is depicted in panels C, F and I (Overlay). Nuclear staining of the polycystin-1 CTT is detected with the specific antibody (D) and not with preimmune serum (G) in the renal tubules of the transgenic mice. Little or no nuclear staining is observed in kidneys from the WT animals (A). (J–O) Higher magnification of the regions outlined in the boxes in panels A–F. Arrows indicate nuclei. Original magnifications, ×200 (A–I) and ×750 (J–O).