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. 1996 Dec 15;98(12):2674–2682. doi: 10.1172/JCI119090

Identification and localization of polycystin, the PKD1 gene product.

L Geng 1, Y Segal 1, B Peissel 1, N Deng 1, Y Pei 1, F Carone 1, H G Rennke 1, A M Glücksmann-Kuis 1, M C Schneider 1, M Ericsson 1, S T Reeders 1, J Zhou 1
PMCID: PMC507729  PMID: 8981910

Abstract

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.

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Selected References

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  1. Baert L. Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease. Kidney Int. 1978 Jun;13(6):519–525. doi: 10.1038/ki.1978.75. [DOI] [PubMed] [Google Scholar]
  2. Carone F. A., Bacallao R., Kanwar Y. S. Biology of polycystic kidney disease. Lab Invest. 1994 Apr;70(4):437–448. [PubMed] [Google Scholar]
  3. Daoust M. C., Reynolds D. M., Bichet D. G., Somlo S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics. 1995 Feb 10;25(3):733–736. doi: 10.1016/0888-7543(95)80020-m. [DOI] [PubMed] [Google Scholar]
  4. Du J., Wilson P. D. Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol. 1995 Aug;269(2 Pt 1):C487–C495. doi: 10.1152/ajpcell.1995.269.2.C487. [DOI] [PubMed] [Google Scholar]
  5. Dvergsten J., Manivel J. C., Correa-Rotter R., Rosenberg M. E. Expression of clusterin in human renal diseases. Kidney Int. 1994 Mar;45(3):828–835. doi: 10.1038/ki.1994.109. [DOI] [PubMed] [Google Scholar]
  6. Fossdal R., Böthvarsson M., Asmundsson P., Ragnarsson J., Peters D., Breuning M. H., Jensson O. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis. Hum Genet. 1993 Jul;91(6):609–613. doi: 10.1007/BF00205089. [DOI] [PubMed] [Google Scholar]
  7. Gabow P. A. Autosomal dominant polycystic kidney disease--more than a renal disease. Am J Kidney Dis. 1990 Nov;16(5):403–413. doi: 10.1016/s0272-6386(12)80051-5. [DOI] [PubMed] [Google Scholar]
  8. Gabow P. A., Johnson A. M., Kaehny W. D., Kimberling W. J., Lezotte D. C., Duley I. T., Jones R. H. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311–1319. doi: 10.1038/ki.1992.195. [DOI] [PubMed] [Google Scholar]
  9. Griffiths G., McDowall A., Back R., Dubochet J. On the preparation of cryosections for immunocytochemistry. J Ultrastruct Res. 1984 Oct;89(1):65–78. doi: 10.1016/s0022-5320(84)80024-6. [DOI] [PubMed] [Google Scholar]
  10. Hughes J., Ward C. J., Peral B., Aspinwall R., Clark K., San Millán J. L., Gamble V., Harris P. C. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995 Jun;10(2):151–160. doi: 10.1038/ng0695-151. [DOI] [PubMed] [Google Scholar]
  11. Kimberling W. J., Kumar S., Gabow P. A., Kenyon J. B., Connolly C. J., Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993 Dec;18(3):467–472. doi: 10.1016/s0888-7543(11)80001-7. [DOI] [PubMed] [Google Scholar]
  12. Peral B., Gamble V., San Millán J. L., Strong C., Sloane-Stanley J., Moreno F., Harris P. C. Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. Hum Mol Genet. 1995 Apr;4(4):569–574. doi: 10.1093/hmg/4.4.569. [DOI] [PubMed] [Google Scholar]
  13. Peral B., San Millán J. L., Ong A. C., Gamble V., Ward C. J., Strong C., Harris P. C. Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations. Am J Hum Genet. 1996 Jan;58(1):86–96. [PMC free article] [PubMed] [Google Scholar]
  14. Reeders S. T., Breuning M. H., Davies K. E., Nicholls R. D., Jarman A. P., Higgs D. R., Pearson P. L., Weatherall D. J. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. doi: 10.1038/317542a0. [DOI] [PubMed] [Google Scholar]
  15. Reeders S. T., Zerres K., Gal A., Hogenkamp T., Propping P., Schmidt W., Waldherr R., Dolata M. M., Davies K. E., Weatherall D. J. Prenatal diagnosis of autosomal dominant polycystic kidney disease with a DNA probe. Lancet. 1986 Jul 5;2(8497):6–8. doi: 10.1016/s0140-6736(86)92557-2. [DOI] [PubMed] [Google Scholar]
  16. Turco A. E., Rossetti S., Bresin E., Corra S., Gammaro L., Maschio G., Pignatti P. F. A novel nonsense mutation in the PKD1 gene (C3817T) is associated with autosomal dominant polycystic kidney disease (ADPKD) in a large three-generation Italian family. Hum Mol Genet. 1995 Aug;4(8):1331–1335. doi: 10.1093/hmg/4.8.1331. [DOI] [PubMed] [Google Scholar]
  17. Ward C. J., Turley H., Ong A. C., Comley M., Biddolph S., Chetty R., Ratcliffe P. J., Gattner K., Harris P. C. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1524–1528. doi: 10.1073/pnas.93.4.1524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wilson P. D., Falkenstein D. The pathology of human renal cystic disease. Curr Top Pathol. 1995;88:1–50. doi: 10.1007/978-3-642-79517-6_1. [DOI] [PubMed] [Google Scholar]
  19. Wilson P. D., Sherwood A. C., Palla K., Du J., Watson R., Norman J. T. Reversed polarity of Na(+) -K(+) -ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia. Am J Physiol. 1991 Mar;260(3 Pt 2):F420–F430. doi: 10.1152/ajprenal.1991.260.3.F420. [DOI] [PubMed] [Google Scholar]

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