RIP-ed and ready to dance: new mechanisms for polycystin-1 signaling.
Polycystin-1, the protein encoded by the principal gene involved in autosomal dominant polycystic kidney disease, has been implicated in extracellular sensing as well as in cell-cell and cell-matrix interactions. However, the precise mechanisms involved in polycystin-1 signaling are not well defined. A report in this issue of the JCI demonstrates that the C-terminal tail of polycystin-1 is cleaved from the membrane through regulated intramembrane proteolysis (RIP) and that this domain translocates to the nucleus, where it activates the AP-1 transcription pathway. This translocation appears to be modulated by polycystin-2, with which polycystin-1 is thought to interact. These findings provide what we believe to be the first evidence that polycystin-1 can signal directly to the nucleus and that polycystin-1-polycystin-2 interactions do not require colocalization of these proteins in the same membrane compartment.
Guay-Woodford
Lisa M
LM
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. lgw@uab.edu
D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D005799:Genes, Dominant; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050396:TRPP Cation Channels; D018808:Transcription Factor AP-1 / Q000378:metabolism
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels; D018808:Transcription Factor AP-1