TRPP channels and polycystins

Advances in Experimental Medicine and Biology

Volumn 704, Issue , 2011, Pages 287-313

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

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

POLYCYSTIN; POLYCYSTIN 1; POLYCYSTIN 2; TRANSCRIPTION FACTOR PAX2; TRANSIENT RECEPTOR POTENTIAL CHANNEL; CALCIUM ION; MEMBRANE PROTEIN; POLYCYSTIC KIDNEY DISEASE 1 LIKE 1 PROTEIN; POLYCYSTIC KIDNEY DISEASE 1 LIKE 2 PROTEIN; POLYCYSTIC KIDNEY DISEASE 1 LIKE 3 PROTEIN; POLYCYSTIC KIDNEY DISEASE RECEPTOR FOR EGG JELLY PROTEIN; POLYCYSTIN 3; POLYCYSTIN 5; UNCLASSIFIED DRUG; POLYCYSTIC KIDNEY DISEASE 1 PROTEIN;

AUTOSOMAL DOMINANT DISORDER; CONFERENCE PAPER; EYE MALFORMATION; GENE; GENE DELETION; GENE MUTATION; HUMAN; INCIDENCE; KIDNEY POLYCYSTIC DISEASE; MALE FERTILITY; MYOPATHY; NONHUMAN; PATHOGENESIS; PC1 GENE; PKD1L1 GENE; PKD1L2 GENE; PKDREJ GENE; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; SITUS INVERSUS; TASTE BUD; TASTE DISCRIMINATION; TRPP1 GENE; TRPP2 GENE; TRPP3 GENE; TRPP5 GENE; ARTICLE; CALCIUM SIGNALING; CALCIUM TRANSPORT; CELL MEMBRANE; CELLULAR DISTRIBUTION; CHEMORECEPTOR CELL; ENDOPLASMIC RETICULUM; EUKARYOTIC FLAGELLUM; EXTRACELLULAR SPACE; MECHANOTRANSDUCTION; PKD1 GENE; PKD2 GENE; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; SEQUENCE HOMOLOGY; SPERM; ANIMAL; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; HUMANS; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; TRPP CATION CHANNELS;

EID: 79959794426     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-94-007-0265-3_16     Document Type: Conference Paper

References (193)

1. Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517-524
2. Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387-417
3. Desai BN, Clapham DE (2005) TRP channels and mice deficient in TRP channels. Pflugers Arch 451:11-18
4. Ramsey IS, Delling M, Clapham DE (2006) An introduction to TRP channels. Annu Rev Physiol 68:619-647
5. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: Dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517-529
6. 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
7. 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
8. 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
9. Moiseenkova-Bell VY, Wensel TG (2009) Hot on the trail of TRP channel structure. J Gen Physiol 133:239-244
10. 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
11. Igarashi P, Somlo S (2002) Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 13:2384-2398
12. 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
13. The 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. Cell 77:881-894
14. The International Polycystic Kidney Disease Consortium (1995) Polycystic kidney disease: The complete structure of the PKD1 gene and its protein. Cell 81:289-298
15. Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: The last 3 years. Kidney Int 76:149-168
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. Sutters M, Germino GG (2003) Autosomal dominant polycystic kidney disease: Molecular genetics and pathophysiology. J Lab Clin Med 141:91-101
26. Reeders ST (1992) Multilocus polycystic disease. Nat Genet 1:235-237
27. Pei Y (2001) A two-hit model of cystogenesis in autosomal dominant polycystic kidney disease? Trends Mol Med 7:151-156
28. 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
29. 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 99:194-199
30. Gallagher AR, Hoffmann S, Brown N, Cedzich A, Meruvu S, Podlich D, Feng Y, Könecke V, Vries U, Hammes H, Gretz N, Witzgall R (2006) A truncated polycystin-2 protein causes polycystic kidney disease and retinal degeneration in transgenic rats. J Am Soc Nephrol 17:2719-2730
31. Pei Y, Watnick T (2010) Autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17:115-117
32. 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
33. Gallagher AR, Germino GG, Somlo S (2010) Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17:118-130
34. 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
35. 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
36. 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
37. Hadimeri H, Lamm C, Nyberg G (1998) Coronary aneurysms in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 9:837-841
38. Schievink WI, Huston J, Torres VE, Marsh WR (1995) Intracranial cysts in autosomal dominant polycystic kidney disease. J Neurosurg 83:1004-1007
39. Leung GKK, Fan YW(2005) Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD). J Clin Neurosci 12:817-819
40. Bajwa ZH, Gupta S, Warfield CA, Steinman TI (2001) Pain management in polycystic kidney disease. Kidney Int 60:1631-1644
41. Bajwa ZH, Sial KA, Malik AB, Steinman TI (2004) Pain patterns in patients with polycystic kidney disease. Kidney Int 66:1561-1569
42. Daoust MC, Reynolds DM, Bichet DG, Somlo S (1995) Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics 25:733-736
43. Bogdanova N, Dworniczak B, Dragova D, Todorov V, Dimitrakov D, Kalinov K, Hallmayer J, Horst J, Kalaydjieva L (1995) Genetic heterogeneity of polycystic kidney disease in Bulgaria. Hum Genet 95:645-650
44. Qian F, Noben-Trauth K (2005) Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2). Pflugers Arch 451:277-285
45. 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
46. 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
47. Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321-337
48. Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137:32-45
49. Hildebrandt F, Attanasio M, Otto E (2009) Nephronophthisis:disease mechanisms of a ciliopathy. J Am Soc Nephrol 20:23-35
50. Satir P, Pedersen LB, Christensen ST (2010) The primary cilium at a glance. J Cell Sci 123:499-503
51. Yoder BK, Richards WG, Sweeney WE, Wilkinson JE, Avener ED, Woychik RP (1995) Insertional mutagenesis and molecular analysis of a new gene associated with polycystic kidney disease. Proc Assoc Am Physicians 107:314-323
52. 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
53. Liu W, Murcia NS, Duan Y, Weinbaum S, Yoder BK, Schwiebert E, Satlin LM (2005) Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting duct of monocilium-impaired orpk mice. Am J Physiol Renal Physiol 289:F978-F988
54. Wheatley DN (1995) Primary cilia in normal and pathological tissues. Pathobiology 63: 222-238
55. Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71-79
56. Praetorius HA, Spring KR (2003) Removal of the MDCK cell primary cilium abolishes flow sensing. J Membr Biol 191:69-76
57. Inglis PN, Ou G, Leroux MR, Scholey JM (2007) The sensory cilia of Caenorhabditis elegans. WormBook 1-22
58. Jenkins PM, McEwen DP, Martens JR (2009) Olfactory cilia: Linking sensory cilia function and human disease. Chem Senses 34:451-464
59. Praetorius HA, Spring KR (2005) A physiological view of the primary cilium. Annu Rev Physiol 67:515-529
60. Murcia NS, Richards WG, Yoder BK, Mucenski ML, Dunlap JR, Woychik RP (2000) The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination. Development 127:2347-2355
61. 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
62. 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
63. Zhou J (2009) Polycystins and primary cilia: Primers for cell cycle progression. Annu Rev Physiol 71:83-113
64. 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 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129-137
65. KöttgenM, 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
66. Hogan MC, Manganelli L, Woollard JR, Masyuk AI, Masyuk TV, Tammachote R, Huang BQ, Leontovich AA, Beito TG, Madden BJ, Charlesworth MC, Torres VE, LaRusso NF, Harris PC,Ward CJ (2009) Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol 20:278-288
67. Goetz SC, Anderson KV (2010) The primary cilium: A signalling centre during vertebrate development. Nat Rev Genet 11:331-344
68. 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
69. Giamarchi A, Feng S, Rodat-Despoix L, Xu Y, Bubenshchikova E, Newby LJ, Hao J, Gaudioso C, Crest M, Lupas AN, Honoré 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
70. Petri ET, Celic 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
71. Cantiello HF (2004) Regulation of calcium signaling by polycystin-2. Am J Physiol Renal Physiol 286:F1012-F1029
72. Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M (2004) Polycystins, calcium signaling, and human diseases. Biochem Biophys Res Commun 322:1374-1383
73. Wu G, Hayashi T, Park JH, Dixit M, Reynolds DM, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S (1998) Identification of PKD2L, a human PKD2-related gene: Tissue-specific expression and mapping to chromosome 10q25. Genomics 54:564-568
74. Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T,Weremowicz S, JiW, 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
75. 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
76. Guo L, Schreiber TH, Weremowicz S, Morton CC, Lee C, Zhou J (2000) 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
77. Palmer CP, Aydar E, Djamgoz MBA (2005) A microbial TRP-like polycystic-kidneydisease- related ion channel gene. Biochem J 387:211-219
78. Delmas P, Nauli SM, Li X, Coste B, Osorio N, Crest M, Brown DA, Zhou J (2004) Gating of the polycystin ion channel signaling complex in neurons and kidney cells. FASEB J 18:740-742
79. 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 cationpermeable currents. Nature 408:990-994
80. Köttgen M (2007) TRPP2 and autosomal dominant polycystic kidney disease. Biochim Biophys Acta 1772:836-850
81. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San MillÁn JL, Gamble V, Harris PC (1995) The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet 10:151-160
82. Nims N, Vassmer D, Maser RL (2003) Transmembrane domain analysis of polycystin-1, the product of the polycystic kidney disease-1 (PKD1) gene: Evidence for 11 membranespanning domains. Biochemistry 42:13035-13048
83. Li A, Tian X, Sung S, Somlo S (2003) Identification of two novel polycystic kidney disease- 1-like genes in human and mouse genomes. Genomics 81:596-608
84. Moy GW, Mendoza LM, Schulz JR, Swanson WJ, Glabe CG, Vacquier VD (1996) The sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1. J Cell Biol 133:809-817
85. 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
86. 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
87. 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
88. Yuasa T, Takakura A, Denker BM, Venugopal B, Zhou J (2004) Polycystin-1L2 is a novel G-protein-binding protein. Genomics 84:126-138
89. Barr MM, Sternberg PW (1999) A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 401:386-389
90. Mengerink KJ, Moy GW, Vacquier VD (2002) suREJ3, a polycystin-1 protein, is cleaved at the GPS domain and localizes to the acrosomal region of sea urchin sperm. J Biol Chem 277:943-948
91. 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
92. Delmas P (2004) Polycystins: From mechanosensation to gene regulation. Cell 118: 145-148
93. Delmas P (2005) Polycystins: Polymodal receptor/ion-channel cellular sensors. Pflugers Arch 451:264-276
94. Anyatonwu GI, Ehrlich BE (2004) Calcium signaling and polycystin-2. Biochem Biophys Res Commun 322:1364-1373
95. Somlo S (1999) The PKD2 gene: Structure, interactions, mutations, and inactivation. Adv Nephrol Necker Hosp 29:257-275
96. Somlo S, Ehrlich B (2001) Human disease: Calcium signaling in polycystic kidney disease. Curr Biol 11:R356-R360
97. Giamarchi A, Padilla F, Coste B, Raoux M, Crest M, Honoré E, Delmas P (2006) The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep 7:787-793
98. Nilius B, Voets T, Peters J (2005) TRP channels in disease. Sci STKE 2005:re8
99. Witzgall R (2005) Polycystin-2 - an intracellular or plasma membrane channel? Naunyn Schmiedebergs Arch Pharmacol 371:342-347
100. Köttgen M, Walz G (2005) Subcellular localization and trafficking of polycystins. Pflugers Arch 451:286-293
101. Woudenberg-Vrenken TE, Bindels RJM, Hoenderop JGJ (2009) The role of transient receptor potential channels in kidney disease. Nat Rev Nephrol 5:441-449
102. Tsiokas L (2009) Function and regulation of TRPP2 at the plasma membrane. Am J Physiol Renal Physiol 297:F1-F9
103. Torres VE, Harris PC, Pirson Y (2007) Autosomal dominant polycystic kidney disease. Lancet 369:1287-1301
104. 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
105. 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
106. 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
107. Foggensteiner L, Bevan AP, Thomas R, Coleman N, Boulter C, Bradley J, Ibraghimov- Beskrovnaya O, Klinger K, Sandford R (2000) Cellular and subcellular distribution of polycystin-2, the protein product of the PKD2 gene. J Am Soc Nephrol 11:814-827
108. 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
109. 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
110. 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
111. 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
112. Boletta A, Qian F, Onuchic LF, Bragonzi A, Cortese M, Deen PM, Courtoy PJ, Soria MR, Devuyst O, Monaco L, Germino GG (2001) Biochemical characterization of bona fide polycystin-1 in vitro and in vivo. Am J Kidney Dis 38:1421-1429
113. Sandford R, Sgotto B, Aparicio S, Brenner S, Vaudin M, Wilson RK, Chissoe S, Pepin K, Bateman A, Chothia C, Hughes J, Harris P (1997) Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Hum Mol Genet 6:1483-1489
114. 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 251:625-631
115. Geng L, Segal Y, Peissel B, Deng N, Pei Y, Carone F, Rennke HG, Glücksmann-Kuis AM, Schneider MC, Ericsson M, Reeders ST, Zhou J (1996) Identification and localization of polycystin, the PKD1 gene product. J Clin Invest 98:2674-2682
116. Geng L, Segal Y, Pavlova A, Barros EJ, Löhning C, Lu W, Nigam SK, Frischauf AM, Reeders ST, Zhou J (1997) Distribution and developmentally regulated expression of murine polycystin. Am J Physiol 272:F451-F459
117. 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 104:1459-1468
118. Scheffers MS, van der Bent P, Prins F, Spruit L, Breuning MH, Litvinov SV, de Heer E, Peters DJ (2000) Polycystin-1, the product of the polycystic kidney disease 1 gene, colocalizes with desmosomes in MDCK cells. Hum Mol Genet 9:2743-2750
119. 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 278:36786-36793
120. 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
121. Bai C, Kim S, Li W, Streets AJ, Ong ACM, Tsiokas L (2008) Activation of TRPP2 through mDia1-dependent voltage gating. EMBO J 27:1345-1356
122. Boca M, Distefano G, Qian F, Bhunia AK, Germino GG, Boletta A (2006) Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway. J Am Soc Nephrol 17:637-647
123. Qian Q, Hunter LW, Li M, Marin-Padilla M, Prakash YS, Somlo S, Harris PC, Torres VE, Sieck GC (2003) Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells. Hum Mol Genet 12:1875-1880
124. Aguiari G, Trimi V, Bogo M, Mangolini A, Szabadkai G, Pinton P, Witzgall R, Harris PC, Borea PA, Rizzuto R, del Senno L (2008) Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. Cell Prolif 41:554-573
125. 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
126. Li Q, Dai Y, Guo L, Liu Y, Hao C, Wu G, Basora N, Michalak M, Chen XZ (2003) Polycystin-2 associates with tropomyosin-1, an actin microfilament component. J Mol Biol 325:949-962
127. Li Q, Montalbetti N, Shen PY, Dai X, Cheeseman CI, Karpinski E, Wu G, Cantiello HF, Chen X (2005) Alpha-actinin associates with polycystin-2 and regulates its channel activity. Hum Mol Genet 14:1587-1603
128. Markoff A, Bogdanova N, Knop M, Rüffer C, Kenis H, Lux P, Reutelingsperger C, Todorov V, Dworniczak B, Horst J, Gerke V (2007) Annexin A5 interacts with polycystin-1 and interferes with the polycystin-1 stimulated recruitment of E-cadherin into adherens junctions. J Mol Biol 369:954-966
129. Chen X, Li Q, Wu Y, Liang G, Lara CJ, Cantiello HF (2008) Submembraneous microtubule cytoskeleton: Interaction of TRPP2 with the cell cytoskeleton. FEBS J 275:4675-4683
130. 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
131. 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
132. 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
133. 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
134. Bai C, Giamarchi A, Rodat-Despoix L, Padilla F, Downs T, Tsiokas L, Delmas P (2008) Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits. EMBO Rep 9:472-479
135. 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
136. 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 284:36431-36441
137. 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, Honoré E (2009) Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139:587-596
138. Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, Smedt H de (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
139. 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/80 K-H, the protein mutated in polycystic liver disease, protects polycystin-2/TRPP2 against HERP-mediated degradation. Hum Mol Genet 19:16-24
140. 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 JAKSTAT signaling pathway in a process requiring PKD2. Cell 109:157-168
141. 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 USA 103:5466-5471
142. 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:e9239
143. Shillingford JM, Piontek KB, Germino GG, Weimbs T (2010) Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol 21:489-497
144. Kim E, Arnould T, Sellin LK, Benzing T, Fan MJ, Grüning W, Sokol SY, Drummond I, Walz G (1999) The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 274:4947-4953
145. 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 betacatenin and inhibits canonical Wnt signaling. Hum Mol Genet 17:3105-3117
146. Puri S, Magenheimer BS,Maser RL, Ryan EM, Zien CA,Walker DD,Wallace DP, Hempson SJ, Calvet JP (2004) Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J Biol Chem 279:55455-55464
147. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J (2005) Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 7:1202-1212
148. Park J, Schutzer WE, Lindsley JN, Bagby SP, Oyama TT, Anderson S, Weiss RH (2007) p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: Roscovitine augments p21 levels. BMC Nephrol 8:12
149. Nickel C, Benzing T, Sellin L, Gerke P, Karihaloo A, Liu Z, Cantley LG, Walz G (2002) The polycystin-1 C-terminal fragment triggers branching morphogenesis and migration of tubular kidney epithelial cells. J Clin Invest 109:481-489
150. Banzi M, Aguiari G, Trimi V, Mangolini A, Pinton P, Witzgall R, Rizzuto R, del Senno L (2006) Polycystin-1 promotes PKCalpha-mediated NF-kappaB activation in kidney cells. Biochem Biophys Res Commun 350:257-262
151. 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
152. 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
153. 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
154. Nauli SM, Rossetti S, Kolb RJ, Alenghat FJ, Consugar MB, Harris PC, Ingber DE, Loghman-Adham M, Zhou J (2006) Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol 17:1015-1025
155. Kotsis F, Nitschke R, Boehlke C, Bashkurov M, Walz G, Kuehn EW (2007) Ciliary calcium signaling is modulated by kidney injury molecule-1 (Kim1). Pflugers Arch 453: 819-829
156. Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R (2010) Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development 137:1075-1084
157. 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
158. 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
159. Vandenberg LN, Levin M (2009) Perspectives and open problems in the early phases of left-right patterning. Semin Cell Dev Biol 20:456-463
160. 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
161. 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
162. 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
163. 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
164. Keller SA, Jones JM, Boyle A, Barrow LL, Killen PD, Green DG, Kapousta NV, Hitchcock PF, Swank RT, Meisler MH (1994) Kidney and retinal defects (Krd), a transgene-induced mutation with a deletion of mouse chromosome 19 that includes the Pax2 locus. Genomics 23:309-320
165. Sanyanusin P, McNoe LA, Sullivan MJ, Weaver RG, Eccles MR (1995) Mutation of PAX2 in two siblings with renal-coloboma syndrome. Hum Mol Genet 4:2183-2184
166. Lindemann B (1996) Taste reception. Physiol Rev 76:718-766
167. Roper SD (2007) Signal transduction and information processing in mammalian taste buds. Pflugers Arch 454:759-776
168. Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJP, Zuker CS (2010) The cells and peripheral representation of sodium taste in mice. Nature 464:297-301
169. 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
170. Inada H, Kawabata F, Ishimaru Y, Fushiki T, Matsunami H, Tominaga M (2008) Offresponse property of an acid-activated cation channel complex PKD1L3-PKD2L1. EMBO Rep 9:690-697
171. 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
172. Richter TA, Caicedo A, Roper SD (2003) Sour taste stimuli evoke Ca2+ and pH responses in mouse taste cells. J Physiol (Lond) 547:475-483
173. 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
174. Nelson TM, Lopez Jimenez ND, Tessarollo L, Inoue M, Bachmanov AA, Sullivan SL (2010) Taste Function in Mice with a Targetted Mutation of the Pkd1l3 Gene. Chemical Senses 175. Dotson CD (2010) The search for mechanisms underlying the sour taste evoked by acids continues. Chemical Senses 35:545-547
175. 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
176. Dai X, Karpinski E, Chen X (2006) Permeation and inhibition of polycystin-L channel by monovalent organic cations. Biochim Biophys Acta 1758:197-205
177. Liu Y, Li Q, Tan M, Zhang Y, Karpinski E, Zhou J, Chen X (2002) Modulation of the human polycystin-L channel by voltage and divalent cations. FEBS Lett 525:71-76
178. Li Q, Liu Y, Shen PY, Dai XQ, Wang S, Smillie LB, Sandford R, Chen XZ (2003) Troponin I binds polycystin-L and inhibits its calcium-induced channel. Biochemistry 42:7618-7625
179. Montalbetti N, Li Q, GonzÁlez-Perrett S, Semprine J, Chen X, Cantiello HF (2005) Effect of hydro-osmotic pressure on polycystin-2 channel function in the human syncytiotrophoblast. Pflugers Arch 451:294-303
180. Christensen AP, Corey DP (2007) TRP channels in mechanosensation: Direct or indirect activation? Nat Rev Neurosci 8:510-521
181. 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
182. 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
183. Horner VL,Wolfner MF (2008) Transitioning from egg to embryo: Triggers and mechanisms of egg activation. Dev Dyn 237:527-544
184. 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
185. Butscheid Y, Chubanov V, Steger K, Meyer D, Dietrich A, Gudermann T (2006) Polycystic kidney disease and receptor for egg jelly is a plasma membrane protein of mouse sperm head. Mol Reprod Dev 73:350-360
186. Austin CR (1951) Observations on the penetration of the sperm in the mammalian egg. Aust J Sci Res B 4:581-596
187. Chang MC (1951) Fertilizing capacity of spermatozoa deposited into the fallopian tubes. Nature 168:697-698
188. Ikawa M, Inoue N, Benham AM, Okabe M (2010) Fertilization: A sperm's journey to and interaction with the oocyte. J Clin Invest 120:984-994
189. Sutton KA, Jungnickel MK, Florman HM (2008) A polycystin-1 controls postcopulatory reproductive selection in mice. Proc Natl Acad Sci USA 105:8661-8666
190. 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
191. Karcher C, Fischer A, Schweickert A, Bitzer E, Horie S, Witzgall R, Blum M (2005) Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in nodal cilia. Differentiation 73:425-432
192. Mackenzie FE, Romero R, Williams D, Gillingwater T, Hilton H, Dick J, Riddoch- Contreras J, Wong F, Ireson L, Powles-Glover N, Riley G, Underhill P, Hough T, Arkell R, Greensmith L, Ribchester RR, Blanco G (2009) Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse. Hum Mol Genet 18:3553-3566
193. Blom W, de Muinck Keizer SM, Scholte HR (1981) Acetyl-CoA carboxylase deficiency: An inborn error of de novo fatty acid synthesis. N Engl J Med 305:465-466