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

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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 languageEnglish (US)
Pages (from-to)1433-1443
Number of pages11
JournalJournal of Clinical Investigation
Volume114
Issue number10
DOIs
StatePublished - Nov 2004

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Autosomal Dominant Polycystic Kidney
Cell Communication
Genes
polycystic kidney disease 1 protein
polycystic kidney disease 2 protein

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chauvet, V., Tian, X., Husson, H., Grimm, D. H., Wang, T., Hieseberger, T., ... Caplan, M. J. (2004). Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. Journal of Clinical Investigation, 114(10), 1433-1443. https://doi.org/10.1172/JCI200421753

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

In: Journal of Clinical Investigation, Vol. 114, No. 10, 11.2004, p. 1433-1443.

Research output: Contribution to journalArticle

Chauvet, V, Tian, X, Husson, H, Grimm, DH, Wang, T, Hieseberger, T, Igarashi, P, Bennett, AM, Ibraghimov-Beskrovnaya, O, Somlo, S & Caplan, MJ 2004, 'Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus', Journal of Clinical Investigation, vol. 114, no. 10, pp. 1433-1443. https://doi.org/10.1172/JCI200421753
Chauvet, Veronique ; Tian, Xin ; Husson, Herve ; Grimm, David H. ; Wang, Tong ; Hieseberger, Thomas ; Igarashi, Peter ; Bennett, Anton M. ; Ibraghimov-Beskrovnaya, Oxana ; Somlo, Stefan ; Caplan, Michael J. / Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. In: Journal of Clinical Investigation. 2004 ; Vol. 114, No. 10. pp. 1433-1443.
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