The TRPP subfamily and polycystin-1 proteins

Handbook of Experimental Pharmacology

Volumn 222, Issue , 2014, Pages 675-711

  Semmo, Mariam ^a   Köttgen, Michael ^a   Hofherr, Alexis ^a,b  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Cilia; Polycystic kidney disease; Polycystin physiology; Polycystin 1 proteins; TRPP cation channels

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE ANCHORING PROTEIN; MICRORNA; POLYCYSTIN; POLYCYSTIN 1; POLYCYSTIN 2; TRANSIENT RECEPTOR POTENTIAL CHANNEL; TRPP3 PROTEIN; TRPP5 PROTEIN; UNCLASSIFIED DRUG; POLYCYSTIC KIDNEY DISEASE 1 PROTEIN;

ARTICLE; BRAIN ASYMMETRY; CYTOSKELETON; END STAGE RENAL DISEASE; EUKARYOTIC FLAGELLUM; GENE; GENE EXPRESSION; GENE IDENTIFICATION; GENE LOSS; GENE MUTATION; GENETIC CONSERVATION; HUMAN; KIDNEY POLYCYSTIC DISEASE; MALE FERTILITY; MATING; NONHUMAN; PHENOTYPE; PKD1 GENE; PKD2 GENE; PKD2L1 GENE; PKD2L2 GENE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; SEX DIFFERENCE; SIGNAL TRANSDUCTION; SURVIVAL; ANIMAL; CELL MEMBRANE PERMEABILITY; CHANNEL GATING; CHEMISTRY; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; KNOCKOUT MOUSE; MEMBRANE POTENTIAL; METABOLISM; MOUSE; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL MEMBRANE PERMEABILITY; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; ION CHANNEL GATING; MEMBRANE POTENTIALS; MICE; MICE, KNOCKOUT; PHENOTYPE; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; TRPP CATION CHANNELS;

EID: 84904891505     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-54215-2_27     Document Type: Article

References (264)

1. Anyatonwu GI, Ehrlich BE (2004) Calcium signaling and polycystin-2. Biochem Biophys Res Commun 322:1364–1373.
2. Anyatonwu GI, Estrada M, Tian X, Somlo S, Ehrlich BE (2007) Regulation of ryanodine receptordependent calcium signaling by polycystin-2. Proc Natl Acad Sci USA 104:6454–6459.
3. Audrézet M, Cornec-Le Gall E, Chen J, Redon S, Quéré I, Creff J, Bénech C, Maestri S, Le Meur Y, Férec C (2012) Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat 33:1239–1250.
4. Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM, Baumgarten DA, King BF, Wetzel LH, Kenney PJ, Brummer ME, Bennett WM, Klahr S, Meyers CM, Zhang X, Thompson PA, Miller JP (2006) Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol 1:64–69.
5. Baert L (1978) Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease. Kidney Int 13:519–525.
6. Bajwa ZH, Gupta S, Warfield CA, Steinman TI (2001) Pain management in polycystic kidney disease. Kidney Int 60:1631–1644.
7. Bajwa ZH, Sial KA, Malik AB, Steinman TI (2004) Pain patterns in patients with polycystic kidney disease. Kidney Int 66:1561–1569.
8. Barr MM, Sternberg PW (1999) A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 401:386–389.
9. Basora N, Nomura H, Berger UV, Stayner C, Guo L, Shen X, Zhou J (2002) Tissue and cellular localization of a novel polycystic kidney disease-like gene product, polycystin-L. J Am Soc Nephrol 13:293–301.
10. Bastos AP, Piontek K, Silva AM, Martini D, Menezes LF, Fonseca JM, Fonseca II, Germino GG, Onuchic LF (2009) Pkd1 haploinsufficiency increases renal damage and induces microcyst formation. J Am Soc Nephrol 20:2389–2402.
11. Bataille S, Demoulin N, Devuyst O, Audre´zet M, Dahan K, Godin M, Fonte`sM, Pirson Y, Burtey S (2011) Association of PKD2 (polycystin 2) mutations with left-right laterality defects. Am J Kidney Dis 58:456–460.
12. Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, Helmkamp GM, Grantham JJ (2004) Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int 66:964–973.
13. Bergmann C, Bru¨chle NO, Frank V, Rehder H, Zerres K (2008) Perinatal deaths in a family with autosomal dominant polycystic kidney disease and a PKD2 mutation. N Engl J Med 359: 318–319.
14. Bisgrove BW, Snarr BS, Emrazian A, Yost HJ (2005) Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer’s vesicle are required for specification of the zebrafish left-right axis. Dev Biol 287:274–288.
15. Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Gödel M, Müller K, Herbst M, Hornung M, Doerken M, Köttgen M, Nitschke R, Igarashi P, Walz G, Kuehn EW (2010) Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 12:1115–1122.
16. Boron WF, Boulpaep EL (2009) Medical physiology. A cellular and molecular approach. Saunders/Elsevier, Philadelphia, PA
17. Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R (2001) Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci USA 98:12174–12179.
18. Bui-Xuan E, Li Q, Chen X, Boucher CA, Sandford R, Zhou J, Basora N (2006) More than colocalizing with polycystin-1, polycystin-L is in the centrosome. Am J Physiol Renal Physiol 291:F395–F406.
19. 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 274:28557–28565.
20. Cai Y, Anyatonwu G, Okuhara D, Lee K, Yu Z, Onoe T, Mei C, Qian Q, Geng L, Wiztgall R, Ehrlich BE, Somlo S (2004) Calcium dependence of polycystin-2 channel activity is modulated by phosphorylation at Ser812. J Biol Chem 279:19987–19995.
21. Cantiello HF (2004) Regulation of calcium signaling by polycystin-2. Am J Physiol Renal Physiol 286:F1012–F1029.
22. Ćelić A, Petri ET, Demeler B, Ehrlich BE, Boggon TJ (2008) Domain mapping of the polycystin- 2. C-terminal tail using de novo molecular modeling and biophysical analysis. J Biol Chem 283:28305–28312.
23. Ćelić AS, Petri ET, Benbow J, Hodsdon ME, Ehrlich BE, Boggon TJ (2012) Calcium-induced conformational changes in C-terminal tail of polycystin-2 are necessary for channel gating. J Biol Chem 287:17232–17240.
24. Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190:285–296.
25. Chen XZ, Vassilev PM, Basora N, Peng JB, Nomura H, Segal Y, Brown EM, Reeders ST, Hediger MA, Zhou J (1999) Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature 401:383–386.
26. Chen XZ, Segal Y, Basora N, Guo L, Peng JB, Babakhanlou H, Vassilev PM, Brown EM, Hediger MA, Zhou J (2001) Transport function of the naturally occurring pathogenic polycystin-2 mutant. Biochem Biophys Res Commun 282:1251–1256.
27. Chen Y, Zhang Z, Lv X, Wang Y, Hu Z, Sun H, Tan R, Liu Y, Bian G, Xiao Y, Li Q, Yang Q, Ai J, Feng L, Yang Y, Wei Y, Zhou Q (2008) Expression of Pkd2l2 in testis is implicated in spermatogenesis. Biol Pharm Bull 31:1496–1500.
28. Choi Y, 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 USA 108:10679–10684.
29. Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517–524.
30. Cloonan N, Brown MK, Steptoe AL, Wani S, Chan WL, Forrest ARR, Kolle G, Gabrielli B, Grimmond SM (2008) The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition. Genome Biol 9:R127.
31. Danaci M, Akpolat T, Baştemir M, Sarikaya S, Akan H, Selçuk MB, Cengiz K (1998) The prevalence of seminal vesicle cysts in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 13:2825–2828.
32. Davenport JR, Watts AJ, Roper VC, Croyle MJ, van Groen T, Wyss JM, Nagy TR, Kesterson RA, Yoder BK (2007) Disruption of intraflagellar transport in adult mice leads to obesity and slowonset cystic kidney disease. Curr Biol 17:1586–1594.
33. Davila S, Furu L, Gharavi AG, Tian X, Onoe T, Qian Q, Li A, Cai Y, Kamath PS, King BF, Azurmendi PJ, Tahvanainen P, Käriäinen H, Höckerstedt K, Devuyst O, Pirson Y, Martin RS, Lifton RP, Tahvanainen E, Torres VE, Somlo S (2004) Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet 36:575–577.
34. Delmas P (2004) Polycystins: from mechanosensation to gene regulation. Cell 118:145–148.
35. Delmas P (2005) Polycystins: polymodal receptor/ion-channel cellular sensors. Pflugers Arch 451: 264–276.
36. Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M (2004a) Polycystins, calcium signaling, and human diseases. Biochem Biophys Res Commun 322:1374–1383.
37. Delmas P, Nauli SM, Li X, Coste B, Osorio N, Crest M, Brown DA, Zhou J (2004b) Gating of the polycystin ion channel signaling complex in neurons and kidney cells. FASEB J 18:740–742.
38. Dessauer CW (2009) Adenylyl cyclase–A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Mol Pharmacol 76:935–941.
39. Drenth JPH, te Morsche RHM, Smink R, Bonifacino JS, Jansen JBMJ (2003) Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet 33: 345–347.
40. Du J, Ding M, Sours-Brothers S, Graham S, Ma R (2008) Mediation of angiotensin II-induced Ca2+ signaling by polycystin 2 in glomerular mesangial cells. Am J Physiol Renal Physiol 294: F909–F918.
41. Duning K, Rosenbusch D, Schlüter MA, Tian Y, Kunzelmann K, Meyer N, Schulze U, Markoff A, Pavenstädt H, Weide T (2010) Polycystin-2 activity is controlled by transcriptional coactivator with PDZ binding motif and PALS1-associated tight junction protein. J Biol Chem 285: 33584–33588.
42. European Polycystic Kidney Disease Consortium (1994) The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. The European Polycystic Kidney Disease Consortium. Cell 77:881–894.
43. Fedeles SV, Tian X, Gallagher A, Mitobe M, Nishio S, Lee SH, Cai Y, Geng L, Crews CM, Somlo S (2011) A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet 43: 639–647.
44. Feng S, Okenka GM, Bai CX, Streets AJ, Newby LJ, DeChant BT, Tsiokas L, Obara T, Ong AC (2008) Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2. J Biol Chem 283:28471–28479.
45. Feng S, Rodat-Despoix L, Delmas P, Ong ACM (2011) A single amino acid residue constitutes the third dimerization domain essential for the assembly and function of the tetrameric polycystin- 2 (TRPP2) channel. J Biol Chem 286:18994–19000.
46. Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW (2002) Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis 39:1127–1134.
47. Field S, Riley K, Grimes DT, Hilton H, Simon M, Powles-Glover N, Siggers P, Bogani D, Greenfield A, Norris DP (2011) Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development 138:1131–1142.
48. Fogelgren B, Lin S, Zuo X, Jaffe KM, Park KM, Reichert RJ, Bell PD, Burdine RD, Lipschutz JH (2011) The exocyst protein Sec10 interacts with Polycystin-2 and knockdown causes PKD-phenotypes. PLoS Genet 7:e1001361.
49. Fu X, Wang Y, Schetle N, Gao H, Pütz M, von Gersdorff G, Walz G, Kramer-Zucker AG (2008) The subcellular localization of TRPP2 modulates its function. J Am Soc Nephrol 19: 1342–1351.
50. Gabow PA, Chapman AB, Johnson AM, Tangel DJ, Duley IT, Kaehny WD, Manco-Johnson M, Schrier RW (1990) Renal structure and hypertension in autosomal dominant polycystic kidney disease. Kidney Int 38:1177–1180.
51. Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, Jones RH (1992) Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 41:1311–1319.
52. Gallagher AR, Cedzich A, Gretz N, Somlo S, Witzgall R (2000) The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proc Natl Acad Sci USA 97:4017–4022.
53. Gallio M, Ofstad TA, Macpherson LJ, Wang JW, Zuker CS (2011) The coding of temperature in the Drosophila brain. Cell 144:614–624.
54. Gao Z, Ruden DM, Lu X (2003) PKD2 cation channel is required for directional sperm movement and male fertility. Curr Biol 13:2175–2178.
55. Gao H, Wang Y, Wegierski T, Skouloudaki K, Pütz M, Fu X, Engel C, Boehlke C, Peng H, Kuehn EW, Kim E, Kramer-Zucker A, Walz G (2010) PRKCSH/80K-H, the protein mutated in polycystic liver disease, protects polycystin-2/TRPP2 against HERP-mediated degradation. Hum Mol Genet 19:16–24.
56. Garcia-Gonzalez MA, Outeda P, Zhou Q, Zhou F, Menezes LF, Qian F, Huso DL, Germino GG, Piontek KB, Watnick T (2010) Pkd1 and Pkd2 are required for normal placental development. PLoS One 5(9):e12821.
57. Geng L, Okuhara D, Yu Z, Tian X, Cai Y, Shibazaki S, Somlo S (2006) Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. J Cell Sci 119: 1383–1395.
58. Geng L, Boehmerle W, Maeda Y, Okuhara DY, Tian X, Yu Z, Choe C, Anyatonwu GI, Ehrlich BE, Somlo S (2008) Syntaxin 5 regulates the endoplasmic reticulum channel-release properties of polycystin-2. Proc Natl Acad Sci USA 105:15920–15925.
59. Giamarchi A, Padilla F, Coste B, Raoux M, Crest M, Honore´ E, Delmas P (2006) The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep 7:787–793.
60. Giamarchi A, Feng S, Rodat-Despoix L, Xu Y, Bubenshchikova E, Newby LJ, Hao J, Gaudioso C, Crest M, Lupas AN, Honore´ E, Williamson MP, Obara T, Ong ACM, Delmas P (2010) A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes. EMBO J 29:1176–1191.
61. Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11:331–344.
62. González-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 USA 98:1182–1187.
63. González-Perrett S, Batelli M, Kim K, Essafi M, Timpanaro G, Moltabetti N, Reisin IL, Arnaout MA, Cantiello HF (2002) Voltage dependence and pH regulation of human polycystin-2-mediated cation channel activity. J Biol Chem 277:24959–24966.
64. Grantham JJ (2008) Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 359:1477–1485.
65. Grantham JJ, Chapman AB, Torres VE (2006) Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol 1:148–157.
66. Guo L, Chen M, Basora N, Zhou J (2000a) The human polycystic kidney disease 2-like (PKDL) gene: exon/intron structure and evidence for a novel splicing mechanism. Mamm Genome 11:46–50.
67. Guo L, Schreiber TH, Weremowicz S, Morton CC, Lee C, Zhou J (2000b) Identification and characterization of a novel polycystin family member, polycystin-L2, in mouse and human: sequence, expression, alternative splicing, and chromosomal localization. Genomics 64: 241–251.
68. Hadimeri H, Lamm C, Nyberg G (1998) Coronary aneurysms in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 9:837–841.
69. Hanaoka K, Guggino WB (2000) cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells. J Am Soc Nephrol 11:1179–1187.
70. 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 408:990–994.
71. Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321–337.
72. Harris PC, Bae KT, Rossetti S, Torres VE, Grantham JJ, Chapman AB, Guay-Woodford LM, King BF, Wetzel LH, Baumgarten DA, Kenney PJ, Consugar M, Klahr S, Bennett WM, Meyers CM, Zhang QJ, Thompson PA, Zhu F, Miller JP (2006) Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 17:3013–3019.
73. 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 353:103–107.
74. Hayashi T, Mochizuki T, Reynolds DM, Wu G, Cai Y, Somlo S (1997) Characterization of the exon structure of the polycystic kidney disease 2 gene (PKD2). Genomics 44:131–136.
75. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531.
76. Hidaka S, Könecke V, Osten L, Witzgall R (2004) PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J Biol Chem 279:35009–35016.
77. Hildebrandt F, Otto E (2005) Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet 6:928–940.
78. Hildebrandt F, Benzing T, Katsanis N (2011) Ciliopathies. N Engl J Med 364:1533–1543.
79. Hirokawa N, Tanaka Y, Okada Y, Takeda S (2006) Nodal flow and the generation of left-right asymmetry. Cell 125:33–45.
80. Hoffert JD, Pisitkun T, Wang G, Shen R, Knepper MA (2006) Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc Natl Acad Sci USA 103:7159–7164.
81. Hoffmeister H, Gallagher A, Rascle A, Witzgall R (2011a) The human polycystin-2 protein represents an integral membrane protein with six membrane-spanning domains and intracellular N- and C-termini. Biochem J 433:285–294.
82. Hoffmeister H, Babinger K, Gürster S, Cedzich A, Meese C, Schadendorf K, Osten L, de Vries U, Rascle A, Witzgall R (2011b) Polycystin-2 takes different routes to the somatic and ciliary plasma membrane. J Cell Biol 192:631–645.
83. Hofherr A (2012) The TRPP signaling module: TRPP2/polycystin-1 and TRPP2/PKD1L1. Methods Pharmacol Toxicol 2012:193–219.
84. Hofherr A, Köttgen M (2011) TRPP channels and polycystins. Adv Exp Med Biol 704:287–313.
85. Horio N, Yoshida R, Yasumatsu K, Yanagawa Y, Ishimaru Y, Matsunami H, Ninomiya Y (2011) Sour taste responses in mice lacking PKD channels. PLoS One 6:e20007.
86. Hossack KF, Leddy CL, Johnson AM, Schrier RW, Gabow PA (1988) Echocardiographic findings in autosomal dominant polycystic kidney disease. N Engl J Med 319:907–912.
87. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, Marto JA, Sabatini DM (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332: 1317–1322.
88. Hu J, Barr MM (2005) ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis. Mol Biol Cell 16:458–469.
89. Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Tränkner D, Ryba NJP, Zuker CS (2006) The cells and logic for mammalian sour taste detection. Nature 442:934–938.
90. Huang K, Diener DR, Mitchell A, Pazour GJ, Witman GB, Rosenbaum JL (2007) Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella. J Cell Biol 179:501–514.
91. Huang YA, Maruyama Y, Stimac R, Roper SD (2008) Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste. J Physiol Lond 586:2903–2912.
92. Hughes J, Ward CJ, Aspinwall R, Butler R, Harris PC (1999) Identification of a human homologue of the sea urchin receptor for egg jelly: a polycystic kidney disease-like protein. Hum Mol Genet 8:543–549.
93. Hurd T, Zhou W, Jenkins P, Liu C, Swaroop A, Khanna H, Martens J, Hildebrandt F, Margolis B (2010) The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates ciliamediated vertebrate development. Hum Mol Genet 19:4330–4344.
94. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villén J, Haas W, Sowa ME, Gygi SP (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143:1174–1189.
95. International Polycystic Kidney Disease Consortium (1995) Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium. Cell 81:289–298.
96. Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 103:12569–12574.
97. Jahnel R, Dreger M, Gillen C, Bender O, Kurreck J, Hucho F (2001) Biochemical characterization of the vanilloid receptor 1 expressed in a dorsal root ganglia derived cell line. Eur J Biochem 268:5489–5496.
98. Jurczyk A, Gromley A, Redick S, San Agustin J, Witman G, Pazour GJ, Peters DJM, Doxsey S (2004) Pericentrin forms a complex with intraflagellar transport proteins and polycystin-2 and is required for primary cilia assembly. J Cell Biol 166:637–643.
99. Kamura K, Kobayashi D, Uehara Y, Koshida S, Iijima N, Kudo A, Yokoyama T, Takeda H (2011) Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis. Development 138:1121–1129.
100. Kedei N, Szabo T, Lile JD, Treanor JJ, Olah Z, Iadarola MJ, Blumberg PM (2001) Analysis of the native quaternary structure of vanilloid receptor 1. J Biol Chem 276:28613–28619 702.
101. M. Semmo et al. Kelleher CL, McFann KK, Johnson AM, Schrier RW (2004) Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 17:1029–1034.
102. Khonsari RH, Ohazama A, Raouf R, Kawasaki M, Kawasaki K, Porntaveetus T, Ghafoor S, Hammond P, Suttie M, Odri GA, Sandford RN, Wood JN, Sharpe PT (2013) Multiple postnatal craniofacial anomalies are characterized by conditional loss of polycystic kidney disease 2 (Pkd2). Hum Mol Genet 22:1873–1885.
103. Kim K, Drummond I, Ibraghimov-Beskrovnaya O, Klinger K, Arnaout MA (2000) Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci USA 97:1731–1736.
104. Kim I, Fu Y, Hui K, Moeckel G, Mai W, Li C, Liang D, Zhao P, Ma J, Chen XZ, George AL Jr, Coffey RJ, Feng ZP, Wu G (2008) Fibrocystin/polyductin modulates renal tubular formation by regulating polycystin-2 expression and function. J Am Soc Nephrol 19:455–468.
105. Kimberling WJ, Fain PR, Kenyon JB, Goldgar D, Sujansky E, Gabow PA (1988) Linkage heterogeneity of autosomal dominant polycystic kidney disease. N Engl J Med 319:913–918.
106. King BF, Reed JE, Bergstralh EJ, Sheedy PF, Torres VE (2000) Quantification and longitudinal trends of kidney, renal cyst, and renal parenchyma volumes in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 11:1505–1511.
107. Kobori T, Smith GD, Sandford R, Edwardson JM (2009) The transient receptor potential channels TRPP2 and TRPC1 form a heterotetramer with a 2:2 stoichiometry and an alternating subunit arrangement. J Biol Chem 284:35507–35513.
108. Kotsis F, Boehlke C, Kuehn EW (2013) The ciliary flow sensor and polycystic kidney disease. Nephrol Dial Transplant 28:518–526.
109. Köttgen M (2007) TRPP2 and autosomal dominant polycystic kidney disease. Biochim Biophys Acta 1772:836–850.
110. Köttgen M, Walz G (2005) Subcellular localization and trafficking of polycystins. Pflugers Arch 451:286–293.
111. Köttgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Höpker K, Simmen KC, Tschucke CC, Sandford R, Kim E, Thomas G, Walz G (2005) Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J 24:705–716.
112. Köttgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G (2008) TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol 182:437–447.
113. Köttgen M, Hofherr A, Li W, Chu K, Cook S, Montell C, Watnick T (2011) Drosophila sperm swim backwards in the female reproductive tract and are activated via TRPP2 ion channels. PLoS One 6:e20031.
114. 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 4:191–197.
115. Kuehn EW, Park KM, Somlo S, Bonventre JV (2002) Kidney injury molecule-1 expression in murine polycystic kidney disease. Am J Physiol Renal Physiol 283:F1326–F1336.
116. Langenhan T, Aust G, Hamann J (2013) Sticky signaling–adhesion class g protein-coupled receptors take the stage. Sci Signal 6:re3.
117. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948.
118. Lehtonen S, Ora A, Olkkonen VM, Geng L, Zerial M, Somlo S, Lehtonen E (2000) In vivo interaction of the adapter protein CD2-associated protein with the type 2 polycystic kidney disease protein, polycystin-2. J Biol Chem 275:32888–32893.
119. Leung GKK, Fan YW (2005) Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD). J Clin Neurosci 12:817–819.
120. Li A, Tian X, Sung S, Somlo S (2003a) Identification of two novel polycystic kidney disease-1-like genes in human and mouse genomes. Genomics 81:596–608.
121. Li Q, Dai Y, Guo L, Liu Y, Hao C, Wu G, Basora N, Michalak M, Chen XZ (2003b) Polycystin- 2 associates with tropomyosin-1, an actin microfilament component. J Mol Biol 325:949–962.
122. Li Q, Liu Y, Shen PY, Dai XQ, Wang S, Smillie LB, Sandford R, Chen XZ (2003c) Troponin I binds polycystin-L and inhibits its calcium-induced channel. Biochemistry 42:7618–7625.
123. Li Q, Shen PY, Wu G, Chen XZ (2003d) Polycystin-2 interacts with troponin I, an angiogenesis inhibitor. Biochemistry 42:450–457.
124. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J (2005a) Polycystin-1 and polycystin- 2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 7:1202–1212.
125. Li Y, Wright JM, Qian F, Germino GG, Guggino WB (2005b) Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling. J Biol Chem 280:41298–41306.
126. Li Q, Montalbetti N, Shen PY, Dai X, Cheeseman CI, Karpinski E, Wu G, Cantiello HF, Chen X (2005c) Alpha-actinin associates with polycystin-2 and regulates its channel activity. Hum Mol Genet 14:1587–1603.
127. Li Q, Montalbetti N, Wu Y, Ramos A, Raychowdhury MK, Chen X, Cantiello HF (2006) Polycystin-2 cation channel function is under the control of microtubular structures in primary cilia of renal epithelial cells. J Biol Chem 281:37566–37575.
128. Li Q, Dai X, Shen PY, Wu Y, Long W, Chen CX, Hussain Z, Wang S, Chen X (2007) Direct binding of alpha-actinin enhances TRPP3 channel activity. J Neurochem 103:2391–2400.
129. Li X, Magenheimer BS, Xia S, Johnson T, Wallace DP, Calvet JP, Li R (2008) A tumor necrosis factor-alpha-mediated pathway promoting autosomal dominant. Nat Med 14:863–868.
130. Li M, Yu Y, Yang J (2011) Structural biology of TRP channels. Adv Exp Med Biol 704:1–23.
131. Liang G, Yang J, Wang Z, Li Q, Tang Y, Chen X (2008a) Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha. Hum Mol Genet 17:3254–3262.
132. Liang G, Li Q, Tang Y, Kokame K, Kikuchi T, Wu G, Chen X (2008b) Polycystin-2 is regulated by endoplasmic reticulum-associated degradation. Hum Mol Genet 17:1109–1119.
133. Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LSB, Somlo S, Igarashi P (2003) Kidneyspecific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci USA 100:5286–5291.
134. Longo DL, Harrison TR (2012) Harrison’s principles of internal medicine. McGraw-Hill, New York
135. Lopezjimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98:68–77.
136. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, Larson C, Brent G, Zhou J (1997) Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet 17:179–181.
137. Lu W, Fan X, Basora N, Babakhanlou H, Law T, Rifai N, Harris PC, Perez-Atayde AR, Rennke HG, Zhou J (1999) Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. Nat Genet 21:160–161.
138. Lu W, Shen X, Pavlova A, Lakkis M, Ward CJ, Pritchard L, Harris PC, Genest DR, Perez-Atayde AR, Zhou J (2001) Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet 10:2385–2396.
139. Lumiaho A, Ikäheimo R, Miettinen R, Niemitukia L, Laitinen T, Rantala A, Lampainen E, Laakso M, Hartikainen J (2001) Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1. Am J Kidney Dis 38:1208–1216.
140. Luo Y, Vassilev PM, Li X, Kawanabe Y, Zhou J (2003) Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia. Mol Cell Biol 23:2600–2607.
141. Lyall V, Alam RI, Phan DQ, Ereso GL, Phan TH, Malik SA, Montrose MH, Chu S, Heck GL, Feldman GM, DeSimone JA (2001) Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction. Am J Physiol Cell Physiol 281:C1005–C1013.
142. Ma R, Li W, Rundle D, Kong J, Akbarali HI, Tsiokas L (2005) PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol Cell Biol 25:8285–8298.
143. Magistroni R, He N, Wang K, Andrew R, Johnson A, Gabow P, Dicks E, Parfrey P, Torra R, San-Millan JL, Coto E, van Dijk M, Breuning M, Peters D, Bogdanova N, Ligabue G, Albertazzi A, Hateboer N, Demetriou K, Pierides A, Deltas C, St George-Hyslop P, Ravine D, Pei Y (2003) Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol 14:1164–1174.
144. McGrath J, Somlo S, Makova S, Tian X, Brueckner M (2003) Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114:61–73.
145. Mekahli D, Sammels E, Luyten T, Welkenhuyzen K, van den Heuvel LP, Levtchenko EN, Gijsbers R, Bultynck G, Parys JB, de Smedt H, Missiaen L (2012) Polycystin-1 and polycystin-2 are both required to amplify inositol-trisphosphate-induced Ca2+ release. Cell Calcium 51:452–458.
146. Menezes LF, Germino GG (2009) Polycystic kidney disease, cilia, and planar polarity. Methods Cell Biol 94:273–297.
147. Miyagi K, Kiyonaka S, Yamada K, Miki T, Mori E, Kato K, Numata T, Sawaguchi Y, Numaga T, Kimura T, Kanai Y, Kawano M, Wakamori M, Nomura H, Koni I, Yamagishi M, Mori Y (2009) A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. J Biol Chem 284:34400–34412.
148. 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 272:1339–1342.
149. Moiseenkova-Bell VY, Stanciu LA, Serysheva II, Tobe BJ, Wensel TG (2008) Structure of TRPV1 channel revealed by electron cryomicroscopy. Proc Natl Acad Sci USA 105: 7451–7455.
150. Molina H, Horn DM, Tang N, Mathivanan S, Pandey A (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci USA 104:2199–2204.
151. Molland KL, Paul LN, Yernool DA (1824) Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1. Biochim Biophys Acta 2012: 413–421.
152. Molland KL, Narayanan A, Burgner JW, Yernool DA (2010) Identification of the structural motif responsible for trimeric assembly of the C-terminal regulatory domains of polycystin channels PKD2L1 and PKD2. Biochem J 429:171–183.
153. Moremen KW, Tiemeyer M, NairnAV(2012) Vertebrate protein glycosylation: diversity, synthesis and function. Nat Rev Mol Cell Biol 13:448–462.
154. Murakami M, Ohba T, Xu F, Shida S, Satoh E, Ono K, Miyoshi I, Watanabe H, Ito H, Iijima T (2005) Genomic organization and functional analysis of murine PKD2L1. J Biol Chem 280: 5626–5635.
155. Muto S, Aiba A, Saito Y, Nakao K, Nakamura K, Tomita K, Kitamura T, Kurabayashi M, Nagai R, Higashihara E, Harris PC, Katsuki M, Horie S (2002) Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1. Hum Mol Genet 11:1731–1742.
156. Nauli SM, Zhou J (2004) Polycystins and mechanosensation in renal and nodal cilia. Bioessays 26:844–856.
157. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AEH, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129–137.
158. Neill AT, Moy GW, Vacquier VD (2004) Polycystin-2 associates with the polycystin-1 homolog, suREJ3, and localizes to the acrosomal region of sea urchin spermatozoa. Mol Reprod Dev 67:472–477.
159. Nelson TM, Lopezjimenez ND, Tessarollo L, Inoue M, Bachmanov AA, Sullivan SL (2010) Taste function in mice with a targeted mutation of the Pkd1l3 gene. Chem Senses 35(7):565–577.
160. Newby LJ, Streets AJ, Zhao Y, Harris PC, Ward CJ, Ong AC (2002) Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J Biol Chem 277: 20763–20773.
161. Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
162. Nilius B, Voets T, Peters J (2005) TRP channels in disease. Sci STKE 2005:re8.
163. Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T, Weremowicz S, Ji W, Morton CC, Meisler M, Reeders ST, Zhou J (1998) Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J Biol Chem 273:25967–25973.
164. Norris DP, Grimes DT (2012) Developmental biology. Cilia discern left from right. Science 338: 206–207.
165. Ohta Y, Hartwig JH, Stossel TP (2006) FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling. Nat Cell Biol 8:803–814.
166. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635–648.
167. Orts-Del’immagine A, Wanaverbecq N, Tardivel C, Tillement V, Dallaporta M, Trouslard J (2012) Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem. J Physiol Lond 590:3719–3741.
168. Palmer CP, Aydar E, Djamgoz MBA (2005) A microbial TRP-like polycystic-kidney-diseaserelated ion channel gene. Biochem J 387:211–219.
169. Patel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P (2013) miR-17 92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proc Natl Acad Sci USA 110(26):10765–10770.
170. Paterson AD, Pei Y (1998) Is there a third gene for autosomal dominant polycystic kidney disease? Kidney Int 54:1759–1761.
171. Paterson AD, Wang KR, Lupea D, St George-Hyslop P, Pei Y (2002) Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease. Am J Kidney Dis 40:16–20.
172. Paul BM, Consugar MB, Ryan Lee M, Sundsbak JL, Heyer CM, Rossetti S, Kubly VJ, Hopp K, Torres VE, Coto E, Clementi M, Bogdanova N, de Almeida E, Bichet DG, Harris PC (2014) Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families. Kidney Int 85(2):383–392.
173. Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB, Cole DG (2000) Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol 151:709–718.
174. Pazour GJ, San Agustin JT, Follit JA, Rosenbaum JL, Witman GB (2002) Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr Biol 12:R378–R380.
175. Pei Y (2001) A “two-hit” model of cystogenesis in autosomal dominant polycystic kidney disease? Trends Mol Med 7:151–156.
176. Pei Y, Paterson AD, Wang KR, He N, Hefferton D, Watnick T, Germino GG, Parfrey P, Somlo S, St George-Hyslop P (2001) Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease. Am J Hum Genet 68:355–363.
177. Pennekamp P, Karcher C, Fischer A, Schweickert A, Skryabin B, Horst J, Blum M, Dworniczak B (2002) The ion channel polycystin-2 is required for left-right axis determination in mice. Curr Biol 12:938–943.
178. Persu A, Duyme M, Pirson Y, Lens XM, Messiaen T, Breuning MH, Chauveau D, Levy M, Grünfeld J, Devuyst O (2004) Comparison between siblings and twins supports a role for modifier genes in ADPKD. Kidney Int 66:2132–2136.
179. Peters DJ, Sandkuijl LA (1992) Genetic heterogeneity of polycystic kidney disease in Europe. Contrib Nephrol 97:128–139.
180. Petri ET, Ćelić A, Kennedy SD, Ehrlich BE, Boggon TJ, Hodsdon ME (2010) Structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity. Proc Natl Acad Sci USA 107:9176–9181.
181. Piontek KB, Huso DL, Grinberg A, Liu L, Bedja D, Zhao H, Gabrielson K, Qian F, Mei C, Westphal H, Germino GG (2004) A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol 15:3035–3043.
182. 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: 1490–1495.
183. Plotnikova OV, Pugacheva EN, Golemis EA (2011) Aurora A kinase activity influences calcium signaling in kidney cells. J Cell Biol 193:1021–1032.
184. Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71–79.
185. Praetorius HA, Spring KR (2005) A physiological view of the primary cilium. Annu Rev Physiol 67:515–529.
186. Prasad S, McDaid JP, Tam FW, Haylor JL, Ong AC (2009) Pkd2 dosage influences cellular repair responses following ischemia-reperfusion. Am J Pathol 175:1493–1503.
187. Qian F, Noben-Trauth K (2005) Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2). Pflugers Arch 451:277–285.
188. 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 87:979–987.
189. 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 16:179–183.
190. 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 USA 99:16981–16986.
191. Raychowdhury MK, McLaughlin M, Ramos AJ, Montalbetti N, Bouley R, Ausiello DA, Cantiello HF (2005) Characterization of single channel currents from primary cilia of renal epithelial cells. J Biol Chem 280:34718–34722.
192. Reeders ST (1992) Multilocus polycystic disease. Nat Genet 1:235–237.
193. Reeders ST, Breuning MH, Davies KE, Nicholls RD, Jarman AP, Higgs DR, Pearson PL, Weatherall DJ (1985) A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature 317:542–544.
194. Rosenbaum JL, Witman GB (2002) Intraflagellar transport. Nat Rev Mol Cell Biol 3:813–825.
195. Rossetti S, Burton S, Strmecki L, Pond GR, San Millán 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 13:1230–1237.
196. Rundle DR, Gorbsky G, Tsiokas L (2004) PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1. IN PKD2 localization to mitotic spindles. J Biol Chem 279:29728–29739.
197. Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, de Smedt H (2010) Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J Biol Chem 285:18794–18805.
198. Scheffers MS, Le H, van der Bent P, Leonhard W, Prins F, Spruit L, Breuning MH, de Heer E, Peters DJM (2002) Distinct subcellular expression of endogenous polycystin-2 in the plasma membrane and Golgi apparatus of MDCK cells. Hum Mol Genet 11:59–67.
199. Schievink WI, Huston J, Torres VE, Marsh WR (1995) Intracranial cysts in autosomal dominant polycystic kidney disease. J Neurosurg 83:1004–1007.
200. Schottenfeld J, Sullivan-Brown J, Burdine RD (2007) Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific. Development 134:1605–1615.
201. Sharif-Naeini R, Folgering JHA, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJM, Honore´ E (2009) Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139:587–596.
202. Shimizu T, Janssens A, Voets T, Nilius B (2009) Regulation of the murine TRPP3 channel by voltage, pH, and changes in cell volume. Pflugers Arch 457:795–807.
203. Shimizu T, Higuchi T, Fujii T, Nilius B, Sakai H (2011) Bimodal effect of alkalization on the polycystin transient receptor potential channel, PKD2L1. Pflugers Arch 461:507–513.
204. Sohara E, Luo Y, Zhang J, Manning DK, Beier DR, Zhou J (2008) Nek8 regulates the expression and localization of polycystin-1 and polycystin-2. J Am Soc Nephrol 19:469–476.
205. Somlo S (1999) The PKD2 gene: structure, interactions, mutations, and inactivation. Adv Nephrol Necker Hosp 29:257–275.
206. Somlo S, Ehrlich B (2001) Human disease: calcium signaling in polycystic kidney disease. Curr Biol 11:R356–R360.
207. Stewart AP, Smith GD, Sandford RN, Edwardson JM (2010) Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2-TRPV4 heterotetramer. Biophys J 99:790–797.
208. Streets AJ, Moon DJ, Kane ME, Obara T, Ong ACM (2006) Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro. Hum Mol Genet 15:1465–1473.
209. Streets AJ, Needham AJ, Gill SK, Ong ACM (2010) Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity. Mol Biol Cell 21:3853–3865.
210. Streets AJ, Wessely O, Peters DJM, Ong ACM (2013) Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation. Hum Mol Genet 22:1924–1939.
211. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 101:6062–6067.
212. Sun Z, Amsterdam A, Pazour GJ, Cole DG, Miller MS, Hopkins N (2004) A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney. Development 131: 4085–4093.
213. Sun H, Li QW, Lv XY, Ai JZ, Yang QT, Duan JJ, Bian GH, Xiao Y, Wang YD, Zhang Z, Liu YH, Tan RZ, Yang Y, Wei YQ, Zhou Q (2010) MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. Mol Biol Rep 37(6): 2951–2958.
214. Sutton KA, Jungnickel MK, Ward CJ, Harris PC, Florman HM (2006) Functional characterization of PKDREJ, a male germ cell-restricted polycystin. J Cell Physiol 209:493–500.
215. Taft RA, Denegre JM, Pendola FL, Eppig JJ (2002) Identification of genes encoding mouse oocyte secretory and transmembrane proteins by a signal sequence trap. Biol Reprod 67:953–960.
216. Takakura A, Contrino L, Zhou X, Bonventre JV, Sun Y, Humphreys BD, Zhou J (2009) Renal injury is a third hit promoting rapid development of adult polycystic. Hum Mol Genet 18: 2523–2531.
217. Tarrant MK, Cole PA (2009) The chemical biology of protein phosphorylation. Annu Rev Biochem 78:797–825.
218. Tian Y, Kolb R, Hong J, Carroll J, Li D, You J, Bronson R, Yaffe MB, Zhou J, Benjamin T (2007) TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex. Mol Cell Biol 27:6383–6395.
219. Torra R, Badenas C, Darnell A, Nicolau C, Volpini V, Revert L, Estivill X (1996) Linkage, clinical features, and prognosis of autosomal dominant polycystic kidney disease types 1 and 2. J Am Soc Nephrol 7:2142–2151.
220. Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76:149–168.
221. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407–2418.
222. Tran U, Zakin L, Schweickert A, Agrawal R, Döger R, Blum M, de Robertis EM, Wessely O (2010) The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development 137:1107–1116.
223. Tsiokas L (2009) Function and regulation of TRPP2 at the plasma membrane. Am J Physiol Renal Physiol 297:F1–F9.
224. 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 USA 94: 6965–6970.
225. Tsiokas L, Arnould T, Zhu C, Kim E, Walz G, Sukhatme VP (1999) Specific association of the gene product of PKD2 with the TRPC1 channel. Proc Natl Acad Sci USA 96:3934–3939.
226. U.S. Renal Data System, (2011) Annual data report: Atlas of end-stage renal disease in the United States. National Institutes of Health, Bethesda, MD U.S. Renal Data System (2012) USRDS, annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National Institutes of Health, Bethesda, MD
227. Vassilev PM, Guo L, Chen XZ, Segal Y, Peng JB, Basora N, Babakhanlou H, Cruger G, Kanazirska M (2001) Ye Cp, Brown EM, Hediger MA, Zhou J Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease. Biochem Biophys Res Commun 282:341–350.
228. Veldhuisen B, Spruit L, Dauwerse HG, Breuning MH, Peters DJ (1999) Genes homologous to the autosomal dominant polycystic kidney disease genes (PKD1 and PKD2). Eur J Hum Genet 7:860–872.
229. Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417.
230. Vogel P, Read R, Hansen GM, Freay LC, Zambrowicz BP, Sands AT (2010) Situs inversus in Dpcd/Poll-/-, Nme7-/-, and Pkd1l1-/- mice. Vet Pathol 47:120–131.
231. Volk T, Schwoerer AP, Thiessen S, Schultz J, Ehmke H (2003) A polycystin-2-like large conductance cation channel in rat left ventricular myocytes. Cardiovasc Res 58:76–88.
232. Voronina VA, Takemaru K, Treuting P, Love D, Grubb BR, Hajjar AM, Adams A, Li F, Moon RT (2009) Inactivation of Chibby affects function of motile airway cilia. J Cell Biol 185:225–233.
233. Wang Q, Dai X, Li Q, Wang Z, Cantero Mdel R, Li S, Shen J, Tu J, Cantiello H, Chen X (2012) Structural interaction and functional regulation of polycystin-2 by filamin. PLoS One 7:e40448.
234. 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 2:247–251.
235. Watnick TJ, Jin Y, Matunis E, Kernan MJ, Montell C (2003) A flagellar polycystin-2 homolog required for male fertility in Drosophila. Curr Biol 13:2179–2184.
236. Wegierski T, Steffl D, Kopp C, Tauber R, Buchholz B, Nitschke R, Kuehn EW, Walz G, Köttgen M (2009) TRPP2 channels regulate apoptosis through the Ca2+ concentration in the endoplasmic reticulum. EMBO J 28:490–499.
237. 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: 21729–21737.
238. Wickstead B, Gull K (2011) The evolution of the cytoskeleton. J Cell Biol 194:513–525.
239. Wijdicks EF, Torres VE, Schievink WI (2000) Chronic subdural hematoma in autosomal dominant polycystic kidney disease. Am J Kidney Dis 35:40–43.
240. Wilson PD (2008) Mouse models of polycystic kidney disease. Curr Top Dev Biol 84:311–350.
241. Witzgall R (2005) Polycystin-2–an intracellular or plasma membrane channel? Naunyn Schmiedebergs Arch Pharmacol 371:342–347.
242. Wodarczyk C, Distefano G, Rowe I, Gaetani M, Bricoli B, Muorah M, Spitaleri A, Mannella V, Ricchiuto P, Pema M, Castelli M, Casanova AE, Mollica L, Banzi M, Boca M, Antignac C, Saunier S, Musco G, Boletta A (2010) Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction and regulates the apoptotic response in mammals. PLoS One 5:e12719.
243. Wong W, Scott JD (2004) AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 5:959–970.
244. Woudenberg-Vrenken TE, Bindels RJM, Hoenderop JGJ (2009) The role of transient receptor potential channels in kidney disease. Nat Rev Nephrol 5:441–449.
245. Wu G, Hayashi T, Park JH, Dixit M, Reynolds DM, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S (1998a) Identification of PKD2L, a human PKD2-related gene: tissue-specific expression and mapping to chromosome 10q25. Genomics 54:564–568.
246. Wu G, D’Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H, Kucherlapati R, Edelmann W, Somlo S (1998b) Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 93:177–188.
247. Wu G, Markowitz GS, Li L, D’Agati VD, Factor SM, Geng L, Tibara S, Tuchman J, Cai Y, Park JH, van Adelsberg J, Hou H, Kucherlapati R, Edelmann W, Somlo S (2000) Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nat Genet 24:75–78.
248. Wu G, Tian X, Nishimura S, Markowitz GS, D’Agati V, Park JH, Yao L, Li L, Geng L, Zhao H, Edelmann W, Somlo S (2002) Trans-heterozygous Pkd1 and Pkd2 mutations modify expression of polycystic kidney disease. Hum Mol Genet 11:1845–1854.
249. Wu Y, Dai X, Li Q, Chen CX, Mai W, Hussain Z, Long W, Montalbetti N, Li G, Glynne R, Wang S, Cantiello HF, Wu G, Chen X (2006) Kinesin-2 mediates physical and functional interactions between polycystin-2 and fibrocystin. Hum Mol Genet 15:3280–3292.
250. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss JW, Su AI (2009) BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130.
251. Yang Y, Cochran DA, Gargano MD, King I, Samhat NK, Burger BP, Sabourin KR, Hou Y, Awata J, Parry DAD, Marshall WF, Witman GB, Lu X (2011) Regulation of flagellar motility by the conserved flagellar protein CG34110/Ccdc135/FAP50. Mol Biol Cell 22:976–987.
252. Yang J, Wang Q, Zheng W, Tuli J, Li Q, Wu Y, Hussein S, Dai X, Shafiei S, Li X, Shen PY, Tu J, Chen X (2012) Receptor for activated C kinase 1 (RACK1) inhibits function of transient receptor potential (TRP)-type channel Pkd2L1 through physical interaction. J Biol Chem 287:6551–6561.
253. Ye C, Sun H, Guo W, Wei Y, Zhou Q (2009) Molecular evolution of PKD2 gene family in mammals. Genetica 137:77–86.
254. Yoder BK, Richards WG, Sommardahl C, Sweeney WE, Michaud EJ, Wilkinson JE, Avner ED, Woychik RP (1996) Functional correction of renal defects in a mouse model for ARPKD through expression of the cloned wild-type Tg737 cDNA. Kidney Int 50:1240–1248.
255. 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 13:2508–2516.
256. Yoshiba S, Shiratori H, Kuo IY, Kawasumi A, Shinohara K, Nonaka S, Asai Y, Sasaki G, Belo JA, Sasaki H, Nakai J, Dworniczak B, Ehrlich BE, Pennekamp P, Hamada H (2012) Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2. Science 338: 226–231.
257. Yu S, Hackmann K, Gao J, Gao J, He X, Piontek K, García-González MA, García González 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 USA 104:18688–18693.
258. Yu Y, Ulbrich MH, Li M, Buraei Z, Chen X, Ong ACM, Tong L, Isacoff EY, Yang J (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc Natl Acad Sci USA 106:11558–11563.
259. Yu Y, Ulbrich MH, Li M, Dobbins S, Zhang WK, Tong L, Isacoff EY, Yang J (2012) Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex. Nat Commun 3:1252.
260. Yuasa T, Venugopal B, Weremowicz S, Morton CC, Guo L, Zhou J (2002) The sequence, expression, and chromosomal localization of a novel polycystic kidney disease 1-like gene, PKD1L1, in human. Genomics 79:376–386.
261. Zanivan S, Gnad F, Wickström SA, Geiger T, Macek B, Cox J, Fässler R, Mann M (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J Proteome Res 7:5314–5326.
262. Zhang Y, Wada J, Yasuhara A, Iseda I, Eguchi J, Fukui K, Yang Q, Yamagata K, Hiesberger T, Igarashi P, Zhang H, Wang H, Akagi S, Kanwar YS, Makino H (2007) The role for HNF-1betatargeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells. PLoS One 2:e414.
263. Zhou J (2009) Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol 71:83–113.
264. Zhou A, Hartwig JH, Akyürek LM (2010) Filamins in cell signaling, transcription and organ development. Trends Cell Biol 20:113–123.