Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells.
Mutations in PKD1 and PKD2, the genes that encode polycystin-1 and polycystin-2 respectively, account for almost all cases of autosomal dominant polycystic kidney disease. Although the polycystins are believed to interact in vivo, the two proteins often display dissimilar patterns and gradients of expression during development. In an effort to understand this apparent discrepancy, we investigated how changes in polycystin-2 expression can affect the subcellular localization of polycystin-1. We show that, when polycystin-1 is expressed alone in a PKD2 null cell line, it localizes to the cell surface, as well as to the endoplasmic reticulum. When co-expressed with polycystin-2, however, polycystin-1 is not seen at the cell surface and co-localizes completely with polycystin-2 in the endoplasmic reticulum. The localization of a polycystin-1 fusion protein was similarly affected by changes in its level of expression relative to that of polycystin-2. This phenomenon was observed in populations as well as in individual COS-7 cells. Our data suggest that the localization of polycystin-1 can be regulated via the relative expression level of polycystin-2 in mammalian cells. This mechanism may help to explain the divergent patterns and levels of expression observed for the polycystins, and may provide clues as to how the function of these two proteins are regulated during development.
Grimm
David H
DH
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Cai
Yiqiang
Y
Chauvet
Veronique
V
Rajendran
Vanathy
V
Zeltner
Raoul
R
Geng
Lin
L
Avner
Ellis D
ED
Sweeney
William
W
Somlo
Stefan
S
Caplan
Michael J
MJ
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050396:TRPP Cation Channels; D014162:Transfection
D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050396:TRPP Cation Channels