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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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CHO Cells
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COS Cells
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Cell Line
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Cell Nucleus / metabolism*
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Chlorocebus aethiops
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Cricetinae
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Cricetulus
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Dogs
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Embryo, Mammalian
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Epithelial Cells / cytology
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Kidney Tubules / cytology
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Kidney Tubules / embryology
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Membrane Proteins / metabolism
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Mice
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Mice, Transgenic
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Polycystic Kidney, Autosomal Dominant / genetics
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Polycystic Kidney, Autosomal Dominant / pathology
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Proteins / chemistry*
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Proteins / genetics
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Proteins / metabolism*
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Sequence Deletion
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Signal Transduction*
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Stress, Mechanical
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TRPP Cation Channels
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Transcription Factor AP-1 / metabolism
Substances
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Membrane Proteins
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Proteins
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TRPP Cation Channels
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Transcription Factor AP-1
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polycystic kidney disease 1 protein
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polycystic kidney disease 2 protein