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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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