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J Clin Invest. Dec 15, 1996; 98(12): 2674–2682.
PMCID: PMC507729

Identification and localization of polycystin, the PKD1 gene product.

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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  • Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, Jones RH. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311–1319. [PubMed]
  • Gabow PA. Autosomal dominant polycystic kidney disease--more than a renal disease. Am J Kidney Dis. 1990 Nov;16(5):403–413. [PubMed]
  • Reeders ST, Breuning MH, Davies KE, Nicholls RD, Jarman AP, Higgs DR, Pearson PL, Weatherall DJ. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. [PubMed]
  • Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993 Dec;18(3):467–472. [PubMed]
  • Fossdal R, Böthvarsson M, Asmundsson P, Ragnarsson J, Peters D, Breuning MH, 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. [PubMed]
  • Daoust MC, Reynolds DM, Bichet DG, Somlo S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics. 1995 Feb 10;25(3):733–736. [PubMed]
  • Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995 Jun;10(2):151–160. [PubMed]
  • Griffiths G, McDowall A, Back R, Dubochet J. On the preparation of cryosections for immunocytochemistry. J Ultrastruct Res. 1984 Oct;89(1):65–78. [PubMed]
  • Carone FA, Bacallao R, Kanwar YS. Biology of polycystic kidney disease. Lab Invest. 1994 Apr;70(4):437–448. [PubMed]
  • Wilson PD, Sherwood AC, Palla K, Du J, Watson R, Norman JT. 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. [PubMed]
  • Du J, Wilson PD. 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. [PubMed]
  • Wilson PD, Falkenstein D. The pathology of human renal cystic disease. Curr Top Pathol. 1995;88:1–50. [PubMed]
  • Turco AE, Rossetti S, Bresin E, Corra S, Gammaro L, Maschio G, Pignatti PF. 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. [PubMed]
  • Peral B, San Millán JL, Ong AC, Gamble V, Ward CJ, Strong C, Harris PC. 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]
  • Peral B, Gamble V, San Millán JL, Strong C, Sloane-Stanley J, Moreno F, Harris PC. Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. Hum Mol Genet. 1995 Apr;4(4):569–574. [PubMed]
  • Reeders ST, Zerres K, Gal A, Hogenkamp T, Propping P, Schmidt W, Waldherr R, Dolata MM, Davies KE, Weatherall DJ. Prenatal diagnosis of autosomal dominant polycystic kidney disease with a DNA probe. Lancet. 1986 Jul 5;2(8497):6–8. [PubMed]
  • 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. [PubMed]
  • Dvergsten J, Manivel JC, Correa-Rotter R, Rosenberg ME. Expression of clusterin in human renal diseases. Kidney Int. 1994 Mar;45(3):828–835. [PubMed]
  • Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, Ratcliffe PJ, Gattner K, Harris PC. 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. [PMC free article] [PubMed]

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