Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus.
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.
Chauvet
Veronique
V
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Tian
Xin
X
Husson
Herve
H
Grimm
David H
DH
Wang
Tong
T
Hiesberger
Thomas
T
Hieseberger
Thomas
T
Igarashi
Peter
P
Bennett
Anton M
AM
Ibraghimov-Beskrovnaya
Oxana
O
Somlo
Stefan
S
Caplan
Michael J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000166:cytology; D007684:Kidney Tubules / Q000166:cytology / Q000196:embryology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D013314:Stress, Mechanical; D050396:TRPP Cation Channels; D018808:Transcription Factor AP-1 / Q000378:metabolism
D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels; D018808:Transcription Factor AP-1