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PMID:10770959

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Citation

Foggensteiner, L, Bevan, AP, Thomas, R, Coleman, N, Boulter, C, Bradley, J, Ibraghimov-Beskrovnaya, O, Klinger, K and Sandford, R (2000) Cellular and subcellular distribution of polycystin-2, the protein product of the PKD2 gene. J. Am. Soc. Nephrol. 11:814-27

Abstract

Mutations in the PKD1 and PKD2 genes account for 85 and 15% of cases of autosomal dominant polycystic kidney disease, respectively. Polycystin-2, the product of the PKD2 gene, is predicted to be an integral membrane protein with homology to a family of voltage-activated Ca(2+) channels. In vitro studies suggest that it may interact with polycystin-1, the PKD1 gene product, via coiled-coil domains present in their C-terminal domains. In this study, the cellular and subcellular distribution of polycystin-2 is defined and compared with polycystin-1. A panel of rabbit polyclonal antisera was raised against polycystin-2 and shown to recognize a single band consistent with polycystin-2 in multiple tissues and cell lines by immunoprecipitation and Western blotting. Immunostaining of human and murine renal tissues demonstrated widespread and developmentally regulated expression of polycytin-2, with highest levels in the kidney in the thick ascending limbs of the loop of Henle and the distal convoluted tubule. In contrast, polycystin-1 expression, while localizing to the same tubular segments, was highest in the collecting ducts. Immunohistochemical staining and immunofluorescence microscopy localized polycystin-2 to the basolateral plasma membrane of kidney tubular epithelial cells compared with the junctional localization of polycystin-1. Differences in the developmental, cellular, and subcellular expression of polycystin-1 and polycystin-2 suggest that they may be able to function independently of each other in addition to a potential in vivo interaction via their C-termini.

Links

PubMed

Keywords

Animals; Antibodies/immunology; Blotting, Western; Calcium-Binding Proteins/chemistry; Calcium-Binding Proteins/immunology; Calcium-Binding Proteins/metabolism; Cell Line; Fetus/metabolism; Humans; Kidney/cytology; Kidney/metabolism; Membrane Proteins/chemistry; Membrane Proteins/immunology; Membrane Proteins/metabolism; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Polycystic Kidney, Autosomal Dominant/metabolism; Precipitin Tests; Proteins/chemistry; Proteins/immunology; Proteins/metabolism; Rabbits; TRPP Cation Channels

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PKD2

located_in

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PKD2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKD1

located_in

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKD2

located_in

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKD2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKD2

located_in

GO:0009925: basal plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKD1

part_of

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PKD2

part_of

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PKD2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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