TRPP2 and autosomal dominant polycystic kidney disease

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1772, Issue 8, 2007, Pages 836-850

  Köttgen, Michael ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

ADPKD; Ca2+; Cilia; PKD2; Polycystic kidney disease; Polycystin 2

Indexed keywords

CALCIUM; POLYCYSTIN 2; PROTEASOME INHIBITOR;

APOPTOSIS; AUTOSOMAL DOMINANT DISORDER; CALCIUM CELL LEVEL; CALCIUM SIGNALING; CELL COMPARTMENTALIZATION; CELL MEMBRANE; CELL POLARITY; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CHANNEL GATING; DISEASE COURSE; DRUG MECHANISM; ENDOPLASMIC RETICULUM; EUKARYOTIC FLAGELLUM; GENE ACTIVATION; GENE CONTROL; GENE FUNCTION; GENE IDENTIFICATION; GENE LOCATION; GENE STRUCTURE; GENETIC DISORDER; HUMAN; ION PERMEABILITY; KIDNEY DISEASE; KIDNEY POLYCYSTIC DISEASE; KIDNEY TUBULE; NONHUMAN; PATHOGENESIS; PHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL COMPARTMENTATION; HUMANS; MODELS, BIOLOGICAL; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; SIGNAL TRANSDUCTION; TRPP CATION CHANNELS;

EID: 34547535644     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2007.01.003     Document Type: Review

References (168)

1. Ashcroft F.M. From molecule to malady. Nature 440 (2006) 440-447
2. Gabow P.A. Autosomal dominant polycystic kidney disease. N. Engl. J. Med. 329 (1993) 332-342
3. Wilson P.D. Polycystic kidney disease. N. Engl. J. Med. 350 (2004) 151-164
4. Mochizuki T., Wu G., Hayashi T., Xenophontos S.L., Veldhuisen B., Saris J.J., Reynolds D.M., Cai Y., Gavow P.A., Pierides A., Kimberling W.J., Breuning M.H., C D.C., Peters D.J.M., and Somlo S. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272 (1996) 1339-1342
5. Montell C., Jones K., Hafen E., and Rubin G. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230 (1985) 1040-1043
6. Montell C., and Rubin G.M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2 (1989) 1313-1323
7. Montell C. The TRP superfamily of cation channels. Sci. STKE 2005 (2005) re3
8. Clapham D.E. TRP channels as cellular sensors. Nature 426 (2003) 517-524
9. Sun M., Goldin E., Stahl S., Falardeau J.L., Kennedy J.C., Acierno J.S., Bove C., Kaneski C.R., Nagle J., Bromley M.C., Colman M., Schiffmann R., and Slaugenhaupt S.A. Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Hum. Mol. Genet. 9 (2000) 2471-2478
10. Delmas P. Polycystins: from mechanosensation to gene regulation. Cell 118 (2004) 145-148
11. Delmas P. Polycystins: polymodal receptor/ion-channel cellular sensors. Pflugers Arch. 451 (2005) 264-276
12. Igarashi P., and Somlo S. Genetics and pathogenesis of polycystic kidney disease. J. Am. Soc. Nephrol. 13 (2002) 2384-2398
13. Delmas P., Nauli S.M., Li X., Coste B., Osorio N., Crest M., Brown D.A., and Zhou J. Gating of the polycystin ion channel signaling complex in neurons and kidney cells. FASEB J. 18 (2004) 740-742
14. Hanaoka K., Qian F., Boletta A., Bhunia A.K., Piontek K., Tsiokas L., Sukhatme V.P., Guggino W.B., and Germino G.G. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408 (2000) 990-994
15. Anyatonwu G.I., and Ehrlich B.E. Calcium signaling and polycystin-2. Biochem. Biophys. Res. Commun. 322 (2004) 1364-1373
16. Calvet J.P., and Grantham J.J. The genetics and physiology of polycystic kidney disease. Semin. Nephrol. 21 (2001) 107-123
17. Cantiello H.F. Regulation of calcium signaling by polycystin-2. Am. J. Physiol., Renal Physiol. 286 (2004) F1012-F1029
18. Delmas P., Padilla F., Osorio N., Coste B., Raoux M., and Crest M. Polycystins, calcium signaling, and human diseases. Biochem. Biophys. Res. Commun. 322 (2004) 1374-1383
19. Gallagher A.R., Hidaka S., Gretz N., and Witzgall R. Molecular basis of autosomal-dominant polycystic kidney disease. Cell. Mol. Life Sci. 59 (2002) 682-693
20. Giamarchi A., Padilla F., Coste B., Raoux M., Crest M., Honore E., and Delmas P. The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep. 7 (2006) 787-793
21. Harris P.C. Molecular basis of polycystic kidney disease: PKD1, PKD2 and PKHD1. Curr. Opin. Nephrol. Hypertens. 11 (2002) 309-314
22. Ikeda M., and Guggino W.B. Do polycystins function as cation channels?. Curr. Opin. Nephrol. Hypertens. 11 (2002) 539-545
23. Köttgen M., and Walz G. Subcellular localization and trafficking of polycystins. Pflugers Arch. 451 (2005) 286-293
24. Nilius B., Voets T., and Peters J. TRP channels in disease. Sci. STKE 2005 (2005) re8
25. Pei Y. Molecular genetics of autosomal dominant polycystic kidney disease. Clin. Invest. Med. 26 (2003) 252-258
26. Somlo S. The PKD2 gene: structure, interactions, mutations, and inactivation. Adv. Nephrol. Necker Hosp. 29 (1999) 257-275
27. Somlo S., and Ehrlich B. Human disease: calcium signaling in polycystic kidney disease. Curr. Biol. 11 (2001) R356-R360
28. Witzgall R. Polycystin-2-an intracellular or plasma membrane channel?. Naunyn-Schmiedeberg's Arch. Pharmacol. 371 (2005) 342-347
29. Baert L. Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease. Kidney Int. 13 (1978) 519-525
30. Mochizuki T., Wu G., Hayashi T., Xenophontos S.L., Veldhuisen B., Saris J.J., Reynolds D.M., Cai Y., Gabow P.A., Pierides A., Kimberling W.J., Breuning M.H., Deltas C.C., Peters D.J., and Somlo S. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272 (1996) 1339-1342
31. The-International-Polycystic-Kidney-Disease-Consortium, Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. Cell 81 (1995) 289-298
32. Grantham J.J. 1992 Homer Smith Award. Fluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts. J. Am. Soc. Nephrol. 3 (1993) 1841-1857
33. Sullivan L.P., Wallace D.P., and Grantham J.J. Epithelial transport in polycystic kidney disease. Physiol. Rev. 78 (1998) 1165-1191
34. Boletta A., and Germino G.G. Role of polycystins in renal tubulogenesis. Trends Cell Biol. 13 (2003) 484-492
35. Calvet J.P. Abnormal epithelial cell proliferation in renal cyst formation and growth: the maturation arrest hypothesis. Kidney Int. 47 (1995) 715-732
36. Murcia N.S., Sweeney Jr. W.E., and Avner E.D. New insights into the molecular pathophysiology of polycystic kidney disease [In Process Citation]. Kidney Int. 55 (1999) 1187-1197
37. Nadasdy T., Laszik Z., Lajoie G., Blick K.E., Wheeler D.E., and Silva F.G. Proliferative activity of cyst epithelium in human renal cystic diseases. J. Am. Soc. Nephrol. 5 (1995) 1462-1468
38. Wilson P.D. Epithelial cell polarity and disease. Am. J. Physiol. 272 (1997) F434-F442
39. Pei Y., Watnick T., He N., Wang K., Liang Y., Parfrey P., Germino G., and St George-Hyslop P. Somatic PKD2 mutations in individual kidney and liver cysts support a "two-hit" model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 10 (1999) 1524-1529
40. Qian F., Watnick T.J., Onuchic L.F., and Germino G.G. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 87 (1996) 979-987
41. Hughes J., Ward C.J., Peral B., Aspinwall R., Clark K., San Millan J.L., Gamble V., and Harris P.C. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat. Genet. 10 (1995) 151-160
42. Boletta A., Qian F., Onuchic L.F., Bragonzi A., Cortese M., Deen P.M., Courtoy P.J., Soria M.R., Devuyst O., Monaco L., and Germino G.G. Biochemical characterization of bona fide polycystin-1 in vitro and in vivo. Am. J. Kidney Dis. 38 (2001) 1421-1429
43. Newby L.J., Streets A.J., Zhao Y., Harris P.C., Ward C.J., and Ong A.C. Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J. Biol. Chem. 277 (2002) 20763-20773
44. Qian F., Boletta A., Bhunia A.K., Xu H., Liu L., Ahrabi A.K., Watnick T.J., Zhou F., and Germino G.G. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 16981-16986
45. Sandford R., Sgotto B., Aparicio S., Brenner S., Vaudin M., Wilson R.K., Chissoe S., Pepin K., Bateman A., Chothia C., Hughes J., and Harris P. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Hum. Mol. Genet. 6 (1997) 1483-1489
46. Qian F., Germino F.J., Cai Y., Zhang X., Somlo S., and Germino G.G. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat. Genet. 16 (1997) 179-183
47. Tsiokas L., Kim E., Arnould T., Sukhatme V.P., and Walz G. Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 6965-6970
48. Parnell S.C., Magenheimer B.S., Maser R.L., Rankin C.A., Smine A., Okamoto T., and Calvet J.P. The polycystic kidney disease-1 protein, polycystin-1, binds and activates heterotrimeric G-proteins in vitro. Biochem. Biophys. Res. Commun. 251 (1998) 625-631
49. Delmas P., Nomura H., Li X., Lakkis M., Luo Y., Segal Y., Fernandez-Fernandez J.M., Harris P., Frischauf A.M., Brown D.A., and Zhou J. Constitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2. J. Biol. Chem. 277 (2002) 11276-11283
50. Parnell S.C., Magenheimer B.S., Maser R.L., Zien C.A., Frischauf A.M., and Calvet J.P. Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins. J. Biol. Chem. 277 (2002) 19566-19572
51. Nauli S.M., Alenghat F.J., Luo Y., Williams E., Vassilev P., Li X., Elia A.E., Lu W., Brown E.M., Quinn S.J., Ingber D.E., and Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33 (2003) 129-137
52. Nauli S.M., and Zhou J. Polycystins and mechanosensation in renal and nodal cilia. BioEssays 26 (2004) 844-856
53. Harris P.C. Autosomal dominant polycystic kidney disease: clues to pathogenesis. Hum. Mol. Genet. 8 (1999) 1861-1866
54. Sutters M., and Germino G.G. Autosomal dominant polycystic kidney disease: molecular genetics and pathophysiology. J. Lab. Clin. Med. 141 (2003) 91-101
55. Nomura H., Turco A.E., Pei Y., Kalaydjieva L., Schiavello T., Weremowicz S., Ji W., Morton C.C., Meisler M., Reeders S.T., and Zhou J. 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 (1998) 25967-25973
56. Wu G., Hayashi T., Park J.H., Dixit M., Reynolds D.M., Li L., Maeda Y., Cai Y., Coca-Prados M., and Somlo S. Identification of PKD2L, a human PKD2-related gene: tissue-specific expression and mapping to chromosome 10q25. Genomics 54 (1998) 564-568
57. Guo L., Schreiber T.H., Weremowicz S., Morton C.C., Lee C., and Zhou J. Identification and characterization of a novel polycystin family member, polycystin-L2, in mouse and human: sequence, expression, alternative splicing, and chromosomal localization. Genomics 64 (2000) 241-251
58. Veldhuisen B., Spruit L., Dauwerse H.G., Breuning M.H., and Peters D.J. Genes homologous to the autosomal dominant polycystic kidney disease genes (PKD1 and PKD2). Eur. J. Hum. Genet. 7 (1999) 860-872
59. Palmer C.P., Aydar E., and Djamgoz M.B. A microbial TRP-like polycystic-kidney-disease-related ion channel gene. Biochem. J. 387 (2005) 211-219
60. Neill A.T., Moy G.W., and Vacquier V.D. Polycystin-2 associates with the polycystin-1 homolog, suREJ3, and localizes to the acrosomal region of sea urchin spermatozoa. Mol. Reprod. Dev. 67 (2004) 472-477
61. Barr M.M., DeModena J., Braun D., Nguyen C.Q., Hall D.H., and Sternberg P.W. The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Curr. Biol. 11 (2001) 1341-1346
62. Barr M.M., and Sternberg P.W. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 401 (1999) 386-389
63. Gao Z., Ruden D.M., and Lu X. PKD2 cation channel is required for directional sperm movement and male fertility. Curr. Biol. 13 (2003) 2175-2178
64. Watnick T.J., Jin Y., Matunis E., Kernan M.J., and Montell C. A flagellar polycystin-2 homolog required for male fertility in Drosophila. Curr. Biol. 13 (2003) 2179-2184
65. Bisgrove B.W., Snarr B.S., Emrazian A., and Yost H.J. 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 (2005) 274-288
66. Obara T., Mangos S., Liu Y., Zhao J., Wiessner S., Kramer-Zucker A.G., Olale F., Schier A.F., and Drummond I.A. Polycystin-2 immunolocalization and function in zebrafish. J. Am. Soc. Nephrol. 17 (2006) 2706-2718
67. Sun Z., Amsterdam A., Pazour G.J., Cole D.G., Miller M.S., and Hopkins N. A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney. Development 131 (2004) 4085-4093
68. Wu G., D'Agati V., Cai Y., Markowitz G., Park J.H., Reynolds D.M., Maeda Y., Le T.C., Hou Jr. H., Kucherlapati R., Edelmann W., and Somlo S. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 93 (1998) 177-188
69. Cai Y., Maeda Y., Cedzich A., Torres V.E., Wu G., Hayashi T., Mochizuki T., Park J.H., Witzgall R., and Somlo S. Identification and characterization of polycystin-2, the PKD2 gene product. J. Biol. Chem. 274 (1999) 28557-28565
70. Koulen P., Cai Y., Geng L., Maeda Y., Nishimura S., Witzgall R., Ehrlich B.E., and Somlo S. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4 (2002) 191-197
71. Foggensteiner L., Bevan A.P., Thomas R., Coleman N., Boulter C., Bradley J., Ibraghimov-Beskrovnaya O., Klinger K., and Sandford R. Cellular and subcellular distribution of polycystin-2, the protein product of the PKD2 gene. J. Am. Soc. Nephrol. 11 (2000) 814-827
72. 2+-permeable cation channel in renal epithelia. Mol. Cell. Biol. 23 (2003) 2600-2607
73. Scheffers M.S., Le H., van der Bent P., Leonhard W., Prins F., Spruit L., Breuning M.H., de Heer E., and Peters D.J. Distinct subcellular expression of endogenous polycystin-2 in the plasma membrane and Golgi apparatus of MDCK cells. Hum. Mol. Genet. 11 (2002) 59-67
74. Pazour G.J., San Agustin J.T., Follit J.A., Rosenbaum J.L., and Witman G.B. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12 (2002) R378-R380
75. Jurczyk A., Gromley A., Redick S., San Agustin J., Witman G., Pazour G.J., Peters D.J., and Doxsey S. Pericentrin forms a complex with intraflagellar transport proteins and polycystin-2 and is required for primary cilia assembly. J. Cell Biol. 166 (2004) 637-643
76. Rundle D.R., Gorbsky G., and Tsiokas L. 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 (2004) 29728-29739
77. Chen X.Z., Segal Y., Basora N., Guo L., Peng J.B., Babakhanlou H., Vassilev P.M., Brown E.M., Hediger M.A., and Zhou J. Transport function of the naturally occurring pathogenic polycystin-2 mutant, R742X. Biochem. Biophys. Res. Commun. 282 (2001) 1251-1256
78. 2+ homeostasis in polycystic kidney disease. Biochem. Biophys. Res. Commun. 282 (2001) 341-350
79. 2+-permeable nonselective cation channel. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 1182-1187
80. Chen X.Z., Vassilev P.M., Basora N., Peng J.B., Nomura H., Segal Y., Brown E.M., Reeders S.T., Hediger M.A., and Zhou J. Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature 401 (1999) 383-386
81. Köttgen M., Benzing T., Simmen T., Tauber R., Buchholz B., Feliciangeli S., Huber T.B., Schermer B., Kramer-Zucker A., Hopker K., Simmen K.C., Tschucke C.C., Sandford R., Kim E., Thomas G., and Walz G. Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J. 24 (2005) 705-716
82. Babich V., Zeng W.Z., Yeh B.I., Ibraghimov-Beskrovnaya O., Cai Y., Somlo S., and Huang C.L. The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. J. Biol. Chem. 279 (2004) 25582-25589
83. Pelucchi B., Aguiari G., Pignatelli A., Manzati E., Witzgall R., Del Senno L., and Belluzzi O. Nonspecific cation current associated with native polycystin-2 in HEK-293 cells. J. Am. Soc. Nephrol. 17 (2006) 388-397
84. Torres V.E., and Harris P.C. Mechanisms of Disease: autosomal dominant and recessive polycystic kidney diseases. Nat. Clin. Pract. Nephrol. 2 (2006) 40-55 quiz 55
85. Boca M., Distefano G., Qian F., Bhunia A.K., Germino G.G., and Boletta A. Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway. J. Am. Soc. Nephrol. 17 (2006) 637-647
86. Bhunia A.K., Piontek K., Boletta A., Liu L., Qian F., Xu P.N., Germino F.J., and Germino G.G. PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 109 (2002) 157-168
87. Kim E., Arnould T., Sellin L.K., Benzing T., Fan M.J., Gruning W., Sokol S.Y., Drummond I., and Walz G. The polycystic kidney disease 1 gene product modulates Wnt signaling. J. Biol. Chem. 274 (1999) 4947-4953
88. Shillingford J.M., Murcia N.S., Larson C.H., Low S.H., Hedgepeth R., Brown N., Flask C.A., Novick A.C., Goldfarb D.A., Kramer-Zucker A., Walz G., Piontek K.B., Germino G.G., and Weimbs T. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 5466-5471
89. Puri S., Magenheimer B.S., Maser R.L., Ryan E.M., Zien C.A., Walker D.D., Wallace D.P., Hempson S.J., and Calvet J.P. Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J. Biol. Chem. 279 (2004) 55455-55464
90. Nickel C., Benzing T., Sellin L., Gerke P., Karihaloo A., Liu Z.X., Cantley L.G., and Walz G. The polycystin-1 C-terminal fragment triggers branching morphogenesis and migration of tubular kidney epithelial cells. J. Clin. Invest. 109 (2002) 481-489
91. Berridge M.J., Lipp P., and Bootman M.D. The versatility and universality of calcium signalling. Nat. Rev., Mol. Cell Biol. 1 (2000) 11-21
92. Clapham D.E. Calcium signaling. Cell 80 (1995) 259-268
93. 2+: molecular determinants and functional consequences. Physiol. Rev. 86 (2006) 369-408
94. 2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J. Clin. Invest. 112 (2003) 1906-1914
95. Gallagher A.R., Cedzich A., Gretz N., Somlo S., and Witzgall R. The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 4017-4022
96. Li Q., Dai Y., Guo L., Liu Y., Hao C., Wu G., Basora N., Michalak M., and Chen X.Z. Polycystin-2 associates with tropomyosin-1, an actin microfilament component. J. Mol. Biol. 325 (2003) 949-962
97. Li Q., Montalbetti N., Shen P.Y., Dai X.Q., Cheeseman C.I., Karpinski E., Wu G., Cantiello H.F., and Chen X.Z. Alpha-actinin associates with polycystin-2 and regulates its channel activity. Hum. Mol. Genet. 14 (2005) 1587-1603
98. Hidaka S., Konecke V., Osten L., and Witzgall R. PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J. Biol. Chem. 279 (2004) 35009-35016
99. Lehtonen S., Ora A., Olkkonen V.M., Geng L., Zerial M., Somlo S., and Lehtonen E. In vivo interaction of the adapter protein CD2AP with the type 2 polycystic kidney disease protein, polycystin-2. J. Biol. Chem. (2000)
100. Tsiokas L., Arnould T., Zhu C., Kim E., Walz G., and Sukhatme V.P. Specific association of the gene product of PKD2 with the TRPC1 channel. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 3934-3939
101. Geng L., Okuhara D., Yu Z., Tian X., Cai Y., Shibazaki S., and Somlo S. Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. J. Cell Sci. 119 (2006) 1383-1395
102. Köttgen M., Benzing T., Simmen T., Tauber R., Buchholz B., Feliciangeli S., Huber T.B., Schermer B., Kramer-Zucker A., Hopker K., Simmen K.C., Tschucke C.C., Sandford R., Kim E., Thomas G., and Walz G. Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J. 24 (2005) 705-716
103. Streets A.J., Moon D.J., Kane M.E., Obara T., and Ong A.C. 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 (2006) 1465-1473
104. Volk T., Schwoerer A.P., Thiessen S., Schultz J.H., and Ehmke H. A polycystin-2-like large conductance cation channel in rat left ventricular myocytes. Cardiovasc. Res. 58 (2003) 76-88
105. Mengerink K.J., Moy G.W., and Vacquier V.D. suREJ proteins: new signalling molecules in sea urchin spermatozoa. Zygote 8 Suppl 1 (2000) S28-S30
106. 2+ channels involved in triggering the sea urchin sperm acrosome reaction. J. Biol. Chem. 277 (2002) 1182-1189
107. Moy G.W., Mendoza L.M., Schulz J.R., Swanson W.J., Glabe C.G., and Vacquier V.D. 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 (1996) 809-817
108. Ma R., Li W.P., Rundle D., Kong J., Akbarali H.I., and Tsiokas L. PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol. Cell. Biol. 25 (2005) 8285-8298
109. Jentsch T.J., Hubner C.A., and Fuhrmann J.C. Ion channels: function unravelled by dysfunction. Nat. Cell Biol. 6 (2004) 1039-1047
110. Cai Y., Anyatonwu G., Okuhara D., Lee K.B., Yu Z., Onoe T., Mei C.L., Qian Q., Geng L., Wiztgall R., Ehrlich B.E., and Somlo S. Calcium dependence of polycystin-2 channel activity is modulated by phosphorylation at Ser812. J. Biol. Chem. 279 (2004) 19987-19995
111. 2+ signaling. J. Biol. Chem. 280 (2005) 41298-41306
112. Qian Q., Hunter L.W., Li M., Marin-Padilla M., Prakash Y.S., Somlo S., Harris P.C., Torres V.E., and Sieck G.C. Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells. Hum. Mol. Genet. 12 (2003) 1875-1880
113. Veis D.J., Sorenson C.M., Shutter J.R., and Korsmeyer S.J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75 (1993) 229-240
114. Li A., Davila S., Furu L., Qian Q., Tian X., Kamath P.S., King B.F., Torres V.E., and Somlo S. Mutations in PRKCSH cause isolated autosomal dominant polycystic liver disease. Am. J. Hum. Genet. 72 (2003) 691-703
115. Davila S., Furu L., Gharavi A.G., Tian X., Onoe T., Qian Q., Li A., Cai Y., Kamath P.S., King B.F., Azurmendi P.J., Tahvanainen P., Kaariainen H., Hockerstedt K., Devuyst O., Pirson Y., Martin R.S., Lifton R.P., Tahvanainen E., Torres V.E., and Somlo S. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat. Genet. 36 (2004) 575-577
116. Davenport J.R., and Yoder B.K. An incredible decade for the primary cilium: a look at a once-forgotten organelle. Am. J. Physiol., Renal Physiol. 289 (2005) F1159-F1169
117. Hildebrandt F., and Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease?. Nat. Rev., Genet. 6 (2005) 928-940
118. Zhang Q., Taulman P.D., and Yoder B.K. Cystic kidney diseases: all roads lead to the cilium. Physiology (Bethesda) 19 (2004) 225-230
119. Praetorius H.A., and Spring K.R. A physiological view of the primary cilium. Annu. Rev. Physiol. 67 (2005) 515-529
120. Singla V., and Reiter J.F. The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 313 (2006) 629-633
121. Gong Z., Son W., Chung Y.D., Kim J., Shin D.W., McClung C.A., Lee Y., Lee H.W., Chang D.J., Kaang B.K., Cho H., Oh U., Hirsh J., Kernan M.J., and Kim C. Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila. J. Neurosci. 24 (2004) 9059-9066
122. Kim J., Chung Y.D., Park D.Y., Choi S., Shin D.W., Soh H., Lee H.W., Son W., Yim J., Park C.S., Kernan M.J., and Kim C. A TRPV family ion channel required for hearing in Drosophila. Nature 424 (2003) 81-84
123. Walker R.G., Willingham A.T., and Zuker C.S. A Drosophila mechanosensory transduction channel. Science 287 (2000) 2229-2234
124. Tobin D., Madsen D., Kahn-Kirby A., Peckol E., Moulder G., Barstead R., Maricq A., and Bargmann C. Combinatorial expression of TRPV channel proteins defines their sensory functions and subcellular localization in C. elegans neurons. Neuron 35 (2002) 307-318
125. Pazour G.J., Dickert B.L., Vucica Y., Seeley E.S., Rosenbaum J.L., Witman G.B., and Cole D.G. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151 (2000) 709-718
126. Yoder B.K., Tousson A., Millican L., Wu J.H., Bugg Jr. C.E., Schafer J.A., and Balkovetz D.F. Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. Am. J. Physiol., Renal Physiol. 282 (2002) F541-F552
127. Yoder B.K., Richards W.G., Sweeney W.E., Wilkinson J.E., Avener E.D., and Woychik R.P. Insertional mutagenesis and molecular analysis of a new gene associated with polycystic kidney disease. Proc. Assoc. Am. Physicians 107 (1995) 314-323
128. Yoder B.K., Hou X., and Guay-Woodford L.M. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J. Am. Soc. Nephrol. 13 (2002) 2508-2516
129. Praetorius H.A., and Spring K.R. Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr. Biol. 184 (2001) 71-79
130. Praetorius H.A., and Spring K.R. The renal cell primary cilium functions as a flow sensor. Curr. Opin. Nephrol. Hypertens. 12 (2003) 517-520
131. 2+ concentration is attenuated in collecting duct of monocilium-impaired orpk mice. Am. J. Physiol., Renal Physiol. 289 (2005) F978-F988
132. Raychowdhury M.K., McLaughlin M., Ramos A.J., Montalbetti N., Bouley R., Ausiello D.A., and Cantiello H.F. Characterization of single channel currents from primary cilia of renal epithelial cells. J. Biol. Chem. 280 (2005) 34718-34722
133. Pennekamp P., Karcher C., Fischer A., Schweickert A., Skryabin B., Horst J., Blum M., and Dworniczak B. The ion channel polycystin-2 is required for left-right axis determination in mice. Curr. Biol. 12 (2002) 938-943
134. Hirokawa N., Tanaka Y., Okada Y., and Takeda S. Nodal flow and the generation of left-right asymmetry. Cell 125 (2006) 33-45
135. McGrath J., Somlo S., Makova S., Tian X., and Brueckner M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114 (2003) 61-73
136. Tanaka Y., Okada Y., and Hirokawa N. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435 (2005) 172-177
137. Witzgall R. New developments in the field of cystic kidney diseases. Curr. Mol. Med. 5 (2005) 455-465
138. Li X., Luo Y., Starremans P.G., McNamara C.A., Pei Y., and Zhou J. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat. Cell Biol. 7 (2005) 1202-1212
139. Chauvet V., Tian X., Husson H., Grimm D.H., Wang T., Hiesberger T., Igarashi P., Bennett A.M., Ibraghimov-Beskrovnaya O., Somlo S., and Caplan M.J. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J. Clin. Invest. 114 (2004) 1433-1443
140. Boletta A., Qian F., Onuchic L.F., Bhunia A.K., Phakdeekitcharoen B., Hanaoka K., Guggino W., Monaco L., and Germino G.G. Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol. Cell 6 (2000) 1267-1273
141. Murcia N.S., Sweeney Jr. W.E., and Avner E.D. New insights into the molecular pathophysiology of polycystic kidney disease. Kidney Int. 55 (1999) 1187-1197
142. Edelstein C.L. What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)?. Cell Cycle 4 (2005) 1550-1554
143. Tao Y., Kim J., Faubel S., Wu J.C., Falk S.A., Schrier R.W., and Edelstein C.L. Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 6954-6959
144. Woo D. Apoptosis and loss of renal tissue in polycystic kidney diseases. N. Engl. J. Med. 333 (1995) 18-25
145. Lin H.H., Yang T.P., Jiang S.T., Yang H.Y., and Tang M.J. Bcl-2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation. Kidney Int. 55 (1999) 168-178
146. Orrenius S., Zhivotovsky B., and Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat. Rev., Mol. Cell Biol. 4 (2003) 552-565
147. Rizzuto R., Pinton P., Ferrari D., Chami M., Szabadkai G., Magalhaes P.J., Di Virgilio F., and Pozzan T. Calcium and apoptosis: facts and hypotheses. Oncogene 22 (2003) 8619-8627
148. Szalai G., Krishnamurthy R., and Hajnoczky G. Apoptosis driven by IP(3)-linked mitochondrial calcium signals. EMBO J. 18 (1999) 6349-6361
149. Pinton P., Ferrari D., Rapizzi E., Di Virgilio F., Pozzan T., and Rizzuto R. The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action. EMBO J. 20 (2001) 2690-2701
150. Kip S.N., Hunter L.W., Ren Q., Harris P.C., Somlo S., Torres V.E., Sieck G.C., and Qian Q. [Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype. Circ. Res. 96 (2005) 873-880
151. Köttgen M., Wegierski T., Steffl D., Kopp C., Tauber R., Buchholz B., and Walz G. TRPP2 Regulates the Ca2+ Concentration in the Endoplasmic Reticulum and Controls the Sensitivity to Apoptosis. J. Am. Soc. Nephrol. 17 (2006) SA-O612
152. Grantham J.J., Geiser J.L., and Evan A.P. Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney Int. 31 (1987) 1145-1152
153. Du J., and Wilson P.D. Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am. J. Physiol. 269 (1995) C487-C495
154. Lanoix J., D'Agati V., Szabolcs M., and Trudel M. Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). Oncogene 13 (1996) 1153-1160
155. Arnould T., Sellin L., Benzing T., Tsiokas L., Cohen H.T., Kim E., and Walz G. Cellular activation triggered by the autosomal dominant polycystic kidney disease gene product PKD2. Mol. Cell Biol. 19 (1999) 3423-3434
156. Grimm D.H., Karihaloo A., Cai Y., Somlo S., Cantley L.G., and Caplan M.J. Polycystin-2 regulates proliferation and branching morphogenesis in kidney epithelial cells. J. Biol. Chem. 281 (2006) 137-144
157. Chang M.Y., Parker E., Ibrahim S., Shortland J.R., El Nahas M., Haylor J.L., and Ong A.C. Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models. Nephrol. Dial. Transplant. (2006)
158. 2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells. FASEB J. 18 (2004) 884-886
159. Klein T.J., and Mlodzik M. Planar cell polarization: an emerging model points in the right direction. Annu. Rev. Cell Dev. Biol. 21 (2005) 155-176
160. Germino G.G. Linking cilia to Wnts. Nat. Genet. 37 (2005) 455-457
161. Simons M., and Walz G. Polycystic kidney disease: cell division without a c(l)ue?. Kidney Int. 70 (2006) 854-864
162. Fischer E., Legue E., Doyen A., Nato F., Nicolas J.F., Torres V., Yaniv M., and Pontoglio M. Defective planar cell polarity in polycystic kidney disease. Nat. Genet. 38 (2006) 21-23
163. Simons M., Gloy J., Ganner A., Bullerkotte A., Bashkurov M., Kronig C., Schermer B., Benzing T., Cabello O.A., Jenny A., Mlodzik M., Polok B., Driever W., Obara T., and Walz G. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat. Genet. 37 (2005) 537-543
164. Otto E.A., Schermer B., Obara T., O'Toole J.F., Hiller K.S., Mueller A.M., Ruf R.G., Hoefele J., Beekmann F., Landau D., Foreman J.W., Goodship J.A., Strachan T., Kispert A., Wolf M.T., Gagnadoux M.F., Nivet H., Antignac C., Walz G., Drummond I.A., Benzing T., and Hildebrandt F. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat. Genet. 34 (2003) 413-420
165. Morgan D., Goodship J., Essner J.J., Vogan K.J., Turnpenny L., Yost H.J., Tabin C.J., and Strachan T. The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin. Hum. Genet. 110 (2002) 377-384
166. Torres V.E., Wang X., Qian Q., Somlo S., Harris P.C., and Gattone V.H. 2nd, Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat. Med. 10 (2004) 363-364
167. Harris P.C., and Torres V.E. Understanding pathogenic mechanisms in polycystic kidney disease provides clues for therapy. Curr. Opin. Nephrol. Hypertens. 15 (2006) 456-463
168. Pei Y. A "two-hit" model of cystogenesis in autosomal dominant polycystic kidney disease?. Trends Mol. Med. 7 (2001) 151-156