Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells. J Biol Chem 2003 Sep 19;278(38):36786-93
Date
07/04/2003Pubmed ID
12840011DOI
10.1074/jbc.M306536200Scopus ID
2-s2.0-0141703576 (requires institutional sign-in at Scopus site) 76 CitationsAbstract
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.
Author List
Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, Avner ED, Sweeney W, Somlo S, Caplan MJAuthor
Ellis D. Avner MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
COS Cells
Cell Line
Cell Membrane
Cells, Cultured
DNA, Complementary
Endoplasmic Reticulum
Gene Expression Regulation
Membrane Proteins
Mice
Mice, Transgenic
Microscopy, Fluorescence
Models, Biological
Mutation
Precipitin Tests
Protein Binding
Protein Biosynthesis
Proteins
RNA, Messenger
Recombinant Fusion Proteins
TRPP Cation Channels
Transfection
