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

doi:10.1172/JCI200421753

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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

226 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1433-1443
Number of pages	11
Journal	Journal of Clinical Investigation
Volume	114
Issue number	10
DOIs	https://doi.org/10.1172/JCI200421753
State	Published - Nov 2004

ASJC Scopus subject areas

General Medicine

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title = "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.",

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

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T1 - Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus

AU - Chauvet, Veronique

AU - Tian, Xin

AU - Husson, Herve

AU - Grimm, David H.

AU - Wang, Tong

AU - Hieseberger, Thomas

AU - Igarashi, Peter

AU - Bennett, Anton M.

AU - Ibraghimov-Beskrovnaya, Oxana

AU - Somlo, Stefan

AU - Caplan, Michael J.

PY - 2004/11

Y1 - 2004/11

N2 - 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.

AB - 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.

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

Abstract

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