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) |
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Pages (from-to) | 1433-1443 |
Number of pages | 11 |
Journal | The Journal of clinical investigation |
Volume | 114 |
Issue number | 10 |
DOIs | |
State | Published - Nov 1 2004 |
Externally published | Yes |