TableEdit

Chauvet, V, Tian, X, Husson, H, Grimm, DH, Wang, T, Hiesberger, T, Hieseberger, T, Igarashi, P, Bennett, AM, Ibraghimov-Beskrovnaya, O, Somlo, S and Caplan, MJ (2004) Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J. Clin. Invest. 114:1433-43

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.

PubMed PMC525739 Online version:10.1172/JCI21753

Amino Acid Sequence; Animals; CHO Cells; COS Cells; Cell Line; Cell Nucleus/metabolism; Cercopithecus aethiops; Cricetinae; Cricetulus; Dogs; Embryo, Mammalian; Epithelial Cells/cytology; Kidney Tubules/cytology; Kidney Tubules/embryology; Membrane Proteins/metabolism; Mice; Mice, Transgenic; Polycystic Kidney, Autosomal Dominant/genetics; Polycystic Kidney, Autosomal Dominant/pathology; Proteins/chemistry; Proteins/genetics; Proteins/metabolism; Sequence Deletion; Signal Transduction; Stress, Mechanical; TRPP Cation Channels; Transcription Factor AP-1/metabolism