The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling.
Much of what is known of the activities of polycystin-1 has been inferred from the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear whether the truncation acts like polycystin-1, as a dominant negative, or in unrelated pathways. To address this question, we have examined functional interactions between the intact and truncated forms of polycystin-1 in one cell system. In cells expressing only native polycystin-1, introduction of the truncation replicated the activity of the full-length protein. Conversely, when background levels of polycystin-1 were modestly elevated, the truncation acted as a dominant negative. Hence, the truncation acts in the polycystin pathway, but with effects that depend upon the background level of polycystin-1 expression. Our data raise the possibility that the cytoplasmic carboxyl terminus, either through cleavage products or intramolecular interactions, might feed back to modulate the activity of parent or intact polycystin-1.
Basavanna
Uma
U
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Weber
Kimberly M
KM
Hu
Qinghua
Q
Ziegelstein
Roy C
RC
Germino
Gregory G
GG
Sutters
Michael
M
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D008954:Models, Biological; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000737:chemistry* / Q000378:metabolism*
D002118:Calcium; D050396:TRPP Cation Channels