Mechanical Stimuli Induce Cleavage and Nuclear Translocation of the Polycystin-1 C Terminus

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2004 Nov 17

PMID 15545994

Citations 124

Authors

Veronique Chauvet

Xin Tian

Herve Husson

David H Grimm

Tong Wang

Thomas Hiesberger

Thomas Hieseberger

Peter Igarashi

Anton M Bennett

Oxana Ibraghimov-Beskrovnaya

Stefan Somlo

Michael J Caplan

Affiliations

Soon will be listed here.

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.

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