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Cystogenesis pp 13–22Cite as

Genetic Mechanisms of ADPKD

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 933))

Abstract

Autosomal dominant polycystic kidney disease is caused by mutation of PKD1 (polycystic kidney disease-1) or PKD2 (polycystic kidney disease-2). PKD1 and PKD2 encode PC1 (polycystin-1) and PC2 (polycystin-2), respectively. In addition, the mutation of cilia-associated proteins is also a recognized major factor of pathogenesis, since PC1 and PC2 are located in primary cilium. Abnormalities of PC1 or PC2 lead to aberrant signaling through downstream pathways, such as the negative growth regulation, G protein activation, and canonical and non-canonical Wnt pathways. According to the “second hit” model, an additional somatic mutation results in the expansion of cyst growth. In this chapter we discuss the genetic mechanisms and signaling pathways involved in ADPKD.

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References

  • Anyatonwu GI, Ehrlich BE (2005) Organic cation permeation through the channel formed by polycystin-2. J Biol Chem 280(33):29488–29493. doi:10.1074/jbc.M504359200

    Article  CAS  PubMed  Google Scholar 

  • Anyatonwu GI, Estrada M, Tian X, Somlo S, Ehrlich BE (2007) Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc Natl Acad Sci U S A 104(15):6454–6459. doi:10.1073/pnas.0610324104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babich V, Zeng WZ, Yeh BI, Ibraghimov-Beskrovnaya O, Cai Y, Somlo S, Huang CL (2004) The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. J Biol Chem 279(24):25582–25589. doi:10.1074/jbc.M402829200

    Article  CAS  PubMed  Google Scholar 

  • Banizs B, Komlosi P, Bevensee MO, Schwiebert EM, Bell PD, Yoder BK (2007) Altered pH(i) regulation and Na(+)/HCO3(−) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse. Am J Physiol Cell Physiol 292(4):C1409–C1416. doi:10.1152/ajpcell.00408.2006

    Article  CAS  PubMed  Google Scholar 

  • Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG (2002) PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 109(2):157–168

    Article  CAS  PubMed  Google Scholar 

  • Brasier JL, Henske EP (1997) Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest 99(2):194–199. doi:10.1172/JCI119147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bycroft M, Bateman A, Clarke J, Hamill SJ, Sandford R, Thomas RL, Chothia C (1999) The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease. EMBO J 18(2):297–305. doi:10.1093/emboj/18.2.297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Y, Maeda Y, Cedzich A, Torres VE, Wu G, Hayashi T, Mochizuki T, Park JH, Witzgall R, Somlo S (1999) Identification and characterization of polycystin-2, the PKD2 gene product. J Biol Chem 274(40):28557–28565

    Article  CAS  PubMed  Google Scholar 

  • Casuscelli J, Schmidt S, DeGray B, Petri ET, Celic A, Folta-Stogniew E, Ehrlich BE, Boggon TJ (2009) Analysis of the cytoplasmic interaction between polycystin-1 and polycystin-2. Am J Physiol Renal Physiol 297(5):F1310–F1315. doi:10.1152/ajprenal.00412.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapin HC, Caplan MJ (2010) The cell biology of polycystic kidney disease. J Cell Biol 191(4):701–710. doi:10.1083/jcb.201006173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attie-Bitach T, Guicharnaud L, Devuyst O, Germino GG, Gubler MC (2002) Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development. Am J Pathol 160(3):973–983. doi:10.1016/S0002-9440(10)64919-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi YH, Suzuki A, Hajarnis S, Ma Z, Chapin HC, Caplan MJ, Pontoglio M, Somlo S, Igarashi P (2011) Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proc Natl Acad Sci U S A 108(26):10679–10684. doi:10.1073/pnas.1016214108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornec-Le Gall E, Audrezet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Ferec C, Le Meur Y (2013) Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol JASN 24(6):1006–1013. doi:10.1681/ASN.2012070650

    Article  PubMed  Google Scholar 

  • Delmas P, Nomura H, Li X, Lakkis M, Luo Y, Segal Y, Fernandez-Fernandez JM, Harris P, Frischauf AM, Brown DA, Zhou J (2002) Constitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2. J Biol Chem 277(13):11276–11283. doi:10.1074/jbc.M110483200

    Article  CAS  PubMed  Google Scholar 

  • Dere R, Wilson PD, Sandford RN, Walker CL (2010) Carboxy terminal tail of polycystin-1 regulates localization of TSC2 to repress mTOR. PLoS One 5(2):e9239. doi:10.1371/journal.pone.0009239

    Article  PubMed  PubMed Central  Google Scholar 

  • Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek KB, Germino GG, Pandolfi PP, Boletta A (2009) Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol 29(9):2359–2371. doi:10.1128/MCB.01259-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M (2006) Defective planar cell polarity in polycystic kidney disease. Nat Genet 38(1):21–23. doi:10.1038/ng1701

    Article  CAS  PubMed  Google Scholar 

  • Gallagher AR, Germino GG, Somlo S (2010) Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17(2):118–130. doi:10.1053/j.ackd.2010.01.002

    Article  PubMed  PubMed Central  Google Scholar 

  • Gattone VH 2nd, Wang X, Harris PC, Torres VE (2003) Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 9(10):1323–1326. doi:10.1038/nm935

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Perrett S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, Harris PC, Reisin IL, Arnaout MA, Cantiello HF (2001) Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2 + −permeable nonselective cation channel. Proc Natl Acad Sci U S A 98(3):1182–1187

    Article  CAS  PubMed  Google Scholar 

  • Grantham JJ (1996) The etiology, pathogenesis, and treatment of autosomal dominant polycystic kidney disease: recent advances. Am J Kidney Dis Off J Nat Kidney Found 28(6):788–803

    Article  CAS  Google Scholar 

  • Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, Avner ED, Sweeney W, Somlo S, Caplan MJ (2003) Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells. J Biol Chem 278(38):36786–36793. doi:10.1074/jbc.M306536200

    Article  CAS  PubMed  Google Scholar 

  • Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, Sukhatme VP, Guggino WB, Germino GG (2000) Co-assembly of polycystin-1 and −2 produces unique cation-permeable currents. Nature 408(6815):990–994. doi:10.1038/35050128

    Article  CAS  PubMed  Google Scholar 

  • Harris PC, Ward CJ, Peral B, Hughes J (1995) Polycystic kidney disease. 1: identification and analysis of the primary defect. J Am Soc Nephrol JASN 6(4):1125–1133

    CAS  PubMed  Google Scholar 

  • Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D (1999) Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 353(9147):103–107

    Article  CAS  PubMed  Google Scholar 

  • Hidaka S, Konecke V, Osten L, Witzgall R (2004) PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J Biol Chem 279(33):35009–35016. doi:10.1074/jbc.M314206200

    Article  CAS  PubMed  Google Scholar 

  • Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, Rossetti S, Torres VE, Harris PC (2012) Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest 122(11):4257–4273. doi:10.1172/JCI64313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hovater MB, Olteanu D, Welty EA, Schwiebert EM (2008) Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts. Purinergic Signal 4(2):109–124. doi:10.1007/s11302-008-9102-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huan Y, van Adelsberg J (1999) Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins. J Clin Invest 104(10):1459–1468. doi:10.1172/JCI5111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Manning BD (2008) The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 412(2):179–190. doi:10.1042/BJ20080281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ibraghimov-Beskrovnaya O, Dackowski WR, Foggensteiner L, Coleman N, Thiru S, Petry LR, Burn TC, Connors TD, Van Raay T, Bradley J, Qian F, Onuchic LF, Watnick TJ, Piontek K, Hakim RM, Landes GM, Germino GG, Sandford R, Klinger KW (1997) Polycystin: in vitro synthesis, in vivo tissue expression, and subcellular localization identifies a large membrane-associated protein. Proc Natl Acad Sci U S A 94(12):6397–6402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim I, Ding T, Fu Y, Li C, Cui L, Li A, Lian P, Liang D, Wang DW, Guo C, Ma J, Zhao P, Coffey RJ, Zhan Q, Wu G (2009) Conditional mutation of Pkd2 causes cystogenesis and upregulates beta-catenin. J Am Soc Nephrol JASN 20(12):2556–2569. doi:10.1681/ASN.2009030271

    Article  CAS  PubMed  Google Scholar 

  • Kip SN, Hunter LW, Ren Q, Harris PC, Somlo S, Torres VE, Sieck GC, Qian Q (2005) [Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype. Circ Res 96(8):873–880. doi:10.1161/01.RES.0000163278.68142.8a

    Article  CAS  PubMed  Google Scholar 

  • Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S (2002) Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol 4(3):191–197. doi:10.1038/ncb754

    Article  CAS  PubMed  Google Scholar 

  • Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ (2008) Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling. Hum Mol Genet 17(20):3105–3117. doi:10.1093/hmg/ddn208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Santoso NG, Yu S, Woodward OM, Qian F, Guggino WB (2009) Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling with implications for polycystic kidney disease. J Biol Chem 284(52):36431–36441. doi:10.1074/jbc.M109.068916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang G, Yang J, Wang Z, Li Q, Tang Y, Chen XZ (2008) Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha. Hum Mol Genet 17(20):3254–3262. doi:10.1093/hmg/ddn221

    Article  CAS  PubMed  Google Scholar 

  • Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T (2006) Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 10(1):57–69. doi:10.1016/j.devcel.2005.12.005

    Article  CAS  PubMed  Google Scholar 

  • Masyuk AI, Masyuk TV, Splinter PL, Huang BQ, Stroope AJ, LaRusso NF (2006) Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 131(3):911–920. doi:10.1053/j.gastro.2006.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masyuk TV, Masyuk AI, Torres VE, Harris PC, Larusso NF (2007) Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology 132(3):1104–1116. doi:10.1053/j.gastro.2006.12.039

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, Kimberling WJ, Breuning MH, Deltas CC, Peters DJ, Somlo S (1996) PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272(5266):1339–1342

    Article  CAS  PubMed  Google Scholar 

  • Montesano R, Ghzili H, Carrozzino F, Rossier BC, Feraille E (2009) cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells. Am J Physiol Renal Physiol 296(2):F446–F457. doi:10.1152/ajprenal.90415.2008

    Article  CAS  PubMed  Google Scholar 

  • Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33(2):129–137. doi:10.1038/ng1076

    Article  CAS  PubMed  Google Scholar 

  • Nishio S, Hatano M, Nagata M, Horie S, Koike T, Tokuhisa T, Mochizuki T (2005) Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation. J Clin Invest 115(4):910–918. doi:10.1172/JCI22850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishio S, Tian X, Gallagher AR, Yu Z, Patel V, Igarashi P, Somlo S (2010) Loss of oriented cell division does not initiate cyst formation. J Am Soc Nephrol JASN 21(2):295–302. doi:10.1681/ASN.2009060603

    Article  CAS  PubMed  Google Scholar 

  • Parnell SC, Magenheimer BS, Maser RL, Rankin CA, Smine A, Okamoto T, Calvet JP (1998) The polycystic kidney disease-1 protein, polycystin-1, binds and activates heterotrimeric G-proteins in vitro. Biochem Biophys Res Commun 251(2):625–631. doi:10.1006/bbrc.1998.9514

    Article  CAS  PubMed  Google Scholar 

  • Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St George-Hyslop P (1999) Somatic PKD2 mutations in individual kidney and liver cysts support a “two-hit” model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN 10(7):1524–1529

    CAS  PubMed  Google Scholar 

  • Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, Parfrey P, Germino G, Watnick T (2012) A missense mutation in PKD1 attenuates the severity of renal disease. Kidney Int 81(4):412–417. doi:10.1038/ki.2011.370

    Article  CAS  PubMed  Google Scholar 

  • Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG (2007) A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med 13(12):1490–1495. doi:10.1038/nm1675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Putnam WC, Swenson SM, Reif GA, Wallace DP, Helmkamp GM Jr, Grantham JJ (2007) Identification of a forskolin-like molecule in human renal cysts. J Am Soc Nephrol JASN 18(3):934–943. doi:10.1681/ASN.2006111218

    Article  CAS  PubMed  Google Scholar 

  • Qian F, Watnick TJ, Onuchic LF, Germino GG (1996) The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 87(6):979–987

    Article  CAS  PubMed  Google Scholar 

  • Qian F, Germino FJ, Cai Y, Zhang X, Somlo S, Germino GG (1997) PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet 16(2):179–183. doi:10.1038/ng0697-179

    Article  CAS  PubMed  Google Scholar 

  • Qian F, Boletta A, Bhunia AK, Xu H, Liu L, Ahrabi AK, Watnick TJ, Zhou F, Germino GG (2002) Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc Natl Acad Sci U S A 99(26):16981–16986. doi:10.1073/pnas.252484899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossetti S, Harris PC (2013) The genetics of vascular complications in autosomal dominant polycystic kidney disease (ADPKD). Curr Hypertens Rev 9(1):37–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossetti S, Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, Winearls CG, Harris PC (2002) The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol JASN 13(5):1230–1237

    Article  CAS  PubMed  Google Scholar 

  • Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, Zhang QJ, Thompson PA, Miller JP, Harris PC, Consortium C (2007) Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN 18(7):2143–2160. doi:10.1681/ASN.2006121387

    Article  CAS  PubMed  Google Scholar 

  • Rossetti S, Kubly VJ, Consugar MB, Hopp K, Roy S, Horsley SW, Chauveau D, Rees L, Barratt TM, Van’t Hoff WG, Niaudet P, Torres VE, Harris PC (2009) Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int 75(8):848–855. doi:10.1038/ki.2008.686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, Weimbs T (2006) The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A 103(14):5466–5471. doi:10.1073/pnas.0509694103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M (2012) Altered store operated calcium entry increases cyclic 3′,5′-adenosine monophosphate production and extracellular signal-regulated kinases 1 and 2 phosphorylation in polycystin-2-defective cholangiocytes. Hepatology 55(3):856–868. doi:10.1002/hep.24723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Streets AJ, Wagner BE, Harris PC, Ward CJ, Ong AC (2009) Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J Cell Sci 122(Pt 9):1410–1417. doi:10.1242/jcs.045021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torres VE, Harris PC (2014) Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol JASN 25(1):18–32. doi:10.1681/ASN.2013040398

    Article  CAS  PubMed  Google Scholar 

  • Tsiokas L, Kim E, Arnould T, Sukhatme VP, Walz G (1997) Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. Proc Natl Acad Sci U S A 94(13):6965–6970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vassilev PM, Guo L, Chen XZ, Segal Y, Peng JB, Basora N, Babakhanlou H, Cruger G, Kanazirska M, Ye C, Brown EM, Hediger MA, Zhou J (2001) Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease. Biochem Biophys Res Commun 282(1):341–350. doi:10.1006/bbrc.2001.4554

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Ward CJ, Harris PC, Torres VE (2010) Cyclic nucleotide signaling in polycystic kidney disease. Kidney Int 77(2):129–140. doi:10.1038/ki.2009.438

    Article  CAS  PubMed  Google Scholar 

  • Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, Ratcliffe PJ, Gattner K, Harris PC (1996) 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 93(4):1524–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, Landes G, Germino GG (1998) Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease. Mol Cell 2(2):247–251

    Article  CAS  PubMed  Google Scholar 

  • Wei W, Hackmann K, Xu H, Germino G, Qian F (2007) Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J Biol Chem 282(30):21729–21737. doi:10.1074/jbc.M703218200

    Article  CAS  PubMed  Google Scholar 

  • Xu C, Rossetti S, Jiang L, Harris PC, Brown-Glaberman U, Wandinger-Ness A, Bacallao R, Alper SL (2007) Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling. Am J Physiol Renal Physiol 292(3):F930–F945. doi:10.1152/ajprenal.00285.2006

    Article  CAS  PubMed  Google Scholar 

  • Yoder BK, Hou X, Guay-Woodford LM (2002) The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol JASN 13(10):2508–2516

    Article  CAS  PubMed  Google Scholar 

  • Yu S, Hackmann K, Gao J, He X, Piontek K, Garcia-Gonzalez MA, Menezes LF, Xu H, Germino GG, Zuo J, Qian F (2007) Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proc Natl Acad Sci U S A 104(47):18688–18693. doi:10.1073/pnas.0708217104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang J (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc Natl Acad Sci U S A 106(28):11558–11563. doi:10.1073/pnas.0903684106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Molecular Medicine Laboratory, Department of Life systems, Sookmyung Women’s University, Cheongpa-ro 47-gil 100, Youngsan-gu, Seoul, 04310, South Korea

    Do Yeon Kim

  2. Department of Life systems, Sookmyung Women’s University, Cheongpa-ro 47-gil 100, Youngsan-gu, Seoul, 04310, South Korea

    Jong Hoon Park

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  1. Department of Life systems, Sookmyung Women’s University, Seoul, Korea (Republic of)

    Jong Hoon Park

  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (Republic of)

    Curie Ahn

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Kim, D.Y., Park, J.H. (2016). Genetic Mechanisms of ADPKD. In: Park, J., Ahn, C. (eds) Cystogenesis. Advances in Experimental Medicine and Biology, vol 933. Springer, Singapore. https://doi.org/10.1007/978-981-10-2041-4_2

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