Polycystins and cellular Ca2+ signaling

Cellular and Molecular Life Sciences

Volumn 70, Issue 15, 2013, Pages 2697-2712

  Mekahli, D ^a   Parys, Jan B ^a   Bultynck, G ^a   Missiaen, L ^a   De Smedt, H ^a  

^a LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

Author keywords

ADPKD; Calcium signaling; Polycystin; Renal pathology

Indexed keywords

CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE KINASE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GLYCOGEN SYNTHASE KINASE 3; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; METFORMIN; PHOSPHATIDYLINOSITOL 3 KINASE; POLYCYSTIN; POLYCYSTIN 1; POLYCYSTIN 2; PROTEIN BCL 2; PROTEIN KINASE B; TUBERIN; WNT PROTEIN; B RAF KINASE; CALCIUM; CYCLIC AMP; TARGET OF RAPAMYCIN KINASE;

AMINO TERMINAL SEQUENCE; APOPTOSIS; ATOMIC FORCE MICROSCOPY; BINDING SITE; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; CALCIUM TRANSPORT; CELL INTERACTION; CELL PROLIFERATION; CELL SURVIVAL; CYTOSKELETON; DIMERIZATION; EUKARYOTIC FLAGELLUM; HUMAN; KIDNEY POLYCYSTIC DISEASE; LIPID RAFT; MEMBRANE PERMEABILITY; NONHUMAN; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; RNA INTERFERENCE; SEQUENCE HOMOLOGY; SYNCYTIOTROPHOBLAST; BIOLOGICAL MODEL; INTRACELLULAR MEMBRANE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

APOPTOSIS; CALCIUM; CALCIUM SIGNALING; CELL PROLIFERATION; CYCLIC AMP; HUMANS; INTRACELLULAR MEMBRANES; MODELS, BIOLOGICAL; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; PROTO-ONCOGENE PROTEINS B-RAF; TOR SERINE-THREONINE KINASES; TRPP CATION CHANNELS;

EID: 84880280453     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-012-1188-x     Document Type: Review

References (172)

1. Chang MY, Ong AC (2008) Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol 108:1-7
2. Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321-337
3. Chapin HC, Caplan MJ (2010) The cell biology of polycystic kidney disease. J Cell Biol 191:701-710
4. Hofherr A, Kottgen M (2011) TRPP channels and polycystins. Adv Exp Med Biol 704:287-313
5. Sutters M (2006) The pathogenesis of autosomal dominant polycystic kidney disease. Nephron Exp Nephrol 103:e149-e155
6. Qamar S, Vadivelu M, Sandford R (2007) TRP channels and kidney disease: lessons from polycystic kidney disease. Biochem Soc Trans 35:124-128
7. Kottgen M (2007) TRPP2 and autosomal dominant polycystic kidney disease. Biochim Biophys Acta 1772:836-850
8. Weimbs T (2007) Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. Am J Physiol Renal Physiol 293:F1423-F1432
9. Witzgall R (2007) TRPP2 channel regulation. Handb Exp Pharmacol 179:363-375
10. Tsiokas L, Kim S, Ong EC (2007) Cell biology of polycystin-2. Cell Signal 19:444-453
11. Zhou J (2009) Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol 71:83-113
12. Tsiokas L (2009) Function and regulation of TRPP2 at the plasma membrane. Am J Physiol Renal Physiol 297:F1-F9
13. Gallagher AR, Germino GG, Somlo S (2010) Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17:118-130
14. 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
15. Delmas P (2005) Polycystins: polymodal receptor/ion-channel cellular sensors. Pflugers Arch 451:264-276
16. 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 membrane-spanning domains. Biochemistry 42:13035-13048
17. 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
18. 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
19. 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
20. 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
21. 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
22. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129-137
23. Menezes LF, Germino GG (2009) Polycystic kidney disease, cilia, and planar polarity. Methods Cell Biol 94:273-297
24. 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, co-localizes with desmosomes in MDCK cells. Hum Mol Genet 9:2743-2750
25. 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
26. Scheffers MS, Le H, van der Bent P, Leonhard W, Prins F, Spruit L, Breuning MH, de Heer E, Peters DJ (2002) Distinct subcellular expression of endogenous polycystin-2 in the plasma membrane and Golgi apparatus of MDCK cells. Hum Mol Genet 11:59-67
27. Witzgall R (2005) Polycystin-2-an intracellular or plasma membrane channel? Naunyn Schmiedebergs Arch Pharmacol 371:342-347
28. Kottgen M, Walz G (2005) Subcellular localization and trafficking of polycystins. Pflugers Arch 451:286-293
29. Kottgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Hopker 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
30. Fu X, Wang Y, Schetle N, Gao H, Putz 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
31. Wilson PD (1997) Epithelial cell polarity and disease. Am J Physiol Renal Physiol 272:F434-F442
32. Calvet JP (1993) Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation? Kidney Int 43:101-108
33. Gallagher AR, Hidaka S, Gretz N, Witzgall R (2002) Molecular basis of autosomal-dominant polycystic kidney disease. Cell Mol Life Sci 59:682-693
34. 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
35. Zhang P, Luo Y, Chasan B, Gonzalez-Perrett S, Montalbetti N, Timpanaro GA, Cantero Mdel R, Ramos AJ, Goldmann WH, Zhou J, Cantiello HF (2009) The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1. Hum Mol Genet 18:1238-1251
36. Kottgen 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
37. 2+ signaling. J Biol Chem 280:41298-41306
38. 2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J Biol Chem 285:18794-18805
39. Anyatonwu GI, Estrada M, Tian X, Somlo S, Ehrlich BE (2007) Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc Natl Acad Sci USA 104:6454-6459
40. 2+ signaling with implications for polycystic kidney disease. J Biol Chem 284:36431-36441
41. 2+ entry through interactions with STIM1. PLoS ONE 5:e12305
42. Abdul-Majeed S, Nauli SM (2011) Calcium-mediated mechanisms of cystic expansion. Biochim Biophys Acta 1812:1281-1290
43. 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
44. Praetorius HA, Spring KR (2003) The renal cell primary cilium functions as a flow sensor. Curr Opin Nephrol Hypertens 12:517-520
45. Ong AC, Wheatley DN (2003) Polycystic kidney disease-the ciliary connection. Lancet 361:774-776
46. Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71-79
47. 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
48. Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang J (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc Natl Acad Sci USA 106:11558-11563
49. Zhu J, Yu Y, Ulbrich MH, Li MH, Isacoff EY, Honig B, Yang J (2011) Structural model of the TRPP2/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach. Proc Natl Acad Sci USA 108:10133-10138
50. 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
51. Bai CX, 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
52. 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 AC, Delmas P (2010) A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes. EMBO J 29:1176-1191
53. 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
54. Celic 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
55. 2+-dependent regulation of polycystin-2 channel activity. Proc Natl Acad Sci USA 107:9176-9181
56. Celic 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
57. 2+-permeable nonselective cation channel. Proc Natl Acad Sci USA 98:1182-1187
58. 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
59. Anyatonwu GI, Ehrlich BE (2005) Organic cation permeation through the channel formed by polycystin-2. J Biol Chem 280:29488-29493
60. 2+ homeostasis in polycystic kidney disease. Biochem Biophys Res Commun 282:341-350
61. 2+ signaling by polycystin 2 in glomerular mesangial cells. Am J Physiol Renal Physiol 294:F909-F918
62. 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
63. 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
64. Wang S, Zhang J, Nauli SM, Li X, Starremans PG, Luo Y, Roberts KA, Zhou J (2007) Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia. Mol Cell Biol 27:3241-3252
65. Montalbetti N, Li Q, Gonzalez-Perrett S, Semprine J, Chen XZ, Cantiello HF (2005) Effect of hydro-osmotic pressure on polycystin-2 channel function in the human syncytiotrophoblast. Pflugers Arch 451:294-303
66. Montalbetti N, Li Q, Timpanaro GA, Gonzalez-Perrett S, Dai XQ, Chen XZ, Cantiello HF (2005) Cytoskeletal regulation of calcium-permeable cation channels in the human syncytiotrophoblast: role of gelsolin. J Physiol 566:309-325
67. Montalbetti N, Li Q, Wu Y, Chen XZ, Cantiello HF (2007) Polycystin-2 cation channel function in the human syncytiotrophoblast is regulated by microtubular structures. J Physiol 579:717-728
68. Ma R, Li WP, 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
69. Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS (2006) The cells and logic for mammalian sour taste detection. Nature 442:934-938
70. 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 slow-onset cystic kidney disease. Curr Biol 17:1586-1594
71. 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
72. Dalagiorgou G, Basdra EK, Papavassiliou AG (2010) Polycystin-1: function as a mechanosensor. Int J Biochem Cell Biol 42:1610-1613
73. 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
74. 2+-permeable cation channel in renal epithelia. Mol Cell Biol 23:2600-2607
75. Cai Y, Tang Z (2010) Regulation of ciliary trafficking of polycystin-2 and the pathogenesis of autosomal dominant polycystic kidney disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 35:93-99
76. Hu J, Bae YK, Knobel KM, Barr MM (2006) Casein kinase II and calcineurin modulate TRPP function and ciliary localization. Mol Biol Cell 17:2200-2211
77. Hidaka S, Konecke V, Osten L, Witzgall R (2004) PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J Biol Chem 279:35009-35016
78. Streets AJ, Moon DJ, Kane ME, Obara T, Ong AC (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
79. 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
80. 2+ signaling. Am J Physiol Renal Physiol 292:F930-F945
81. Somlo S, Ehrlich B (2001) Human disease: calcium signaling in polycystic kidney disease. Curr Biol 11:R356-R360
82. 2+ release from intracellular stores in Caenorhabditis elegans. Cell Calcium 37:593-601
83. Cai Y, Anyatonwu G, Okuhara D, Lee KB, Yu Z, Onoe T, Mei CL, 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
84. 2+ storage in health and disease: a dynamic equilibrium. Cell Calcium 47:297-314
85. 2+ concentration in the endoplasmic reticulum. EMBO J 28:490-499
86. Geng L, Boehmerle W, Maeda Y, Okuhara DY, Tian X, Yu Z, Choe CU, 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
87. Xu GM, Gonzalez-Perrett S, Essafi M, Timpanaro GA, Montalbetti N, Arnaout MA, Cantiello HF (2003) Polycystin-1 activates and stabilizes the polycystin-2 channel. J Biol Chem 278:1457-1462
88. Li Q, Montalbetti N, Shen PY, Dai XQ, Cheeseman CI, Karpinski E, Wu G, Cantiello HF, Chen XZ (2005) Alpha-actinin associates with polycystin-2 and regulates its channel activity. Hum Mol Genet 14:1587-1603
89. Bai CX, Kim S, Li WP, Streets AJ, Ong AC, Tsiokas L (2008) Activation of TRPP2 through mDia1-dependent voltage gating. EMBO J 27:1345-1356
90. Wu Y, Dai XQ, Li Q, Chen CX, Mai W, Hussain Z, Long W, Montalbetti N, Li G, Glynne R, Wang S, Cantiello HF, Wu G, Chen XZ (2006) Kinesin-2 mediates physical and functional interactions between polycystin-2 and fibrocystin. Hum Mol Genet 15:3280-3292
91. 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
92. Hooper KM, Boletta A, Germino GG, Hu Q, Ziegelstein RC, Sutters M (2005) Expression of polycystin-1 enhances endoplasmic reticulum calcium uptake and decreases capacitative calcium entry in ATP-stimulated MDCK cells. Am J Physiol Renal Physiol 289:F521-F530
93. Weber KH, Lee EK, Basavanna U, Lindley S, Ziegelstein RC, Germino GG, Sutters M (2008) Heterologous expression of polycystin-1 inhibits endoplasmic reticulum calcium leak in stably transfected MDCK cells. Am J Physiol Renal Physiol 294:F1279-F1286
94. 2+ entry. Am J Physiol Renal Physiol 285:F1168-F1178
95. 2+-dependent pathway(s). Exp Cell Res 304:391-406
96. 2+ release through the PI3 K/Akt pathway. Cell Physiol Biochem 27:715-726
97. 2+ signaling. Cell Calcium 48:161-167
98. Ahrabi AK, Terryn S, Valenti G, Caron N, Serradeil-Le Gal C, Raufaste D, Nielsen S, Horie S, Verbavatz JM, Devuyst O (2007) PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol 18:1740-1753
99. Morel N, Vandenberg G, Ahrabi AK, Caron N, Desjardins F, Balligand JL, Horie S, Devuyst O (2009) PKD1 haploinsufficiency is associated with altered vascular reactivity and abnormal calcium signaling in the mouse aorta. Pflugers Arch 457:845-856
100. 2+ release. Cell Calcium 51:452-458
101. Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76:149-168
102. Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, Helmkamp GM Jr, Grantham JJ (2004) Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int 66:964-973
103. Hanaoka K, Devuyst O, Schwiebert EM, Wilson PD, Guggino WB (1996) A role for CFTR in human autosomal dominant polycystic kidney disease. Am J Physiol Cell Physiol 270:C389-C399
104. Gattone VH 2nd, Wang X, Harris PC, Torres VE (2003) Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 9:1323-1326
105. 2+ and cyclic AMP in neuroendocrine cells. Cell Calcium 51:260-266
106. Choi YH, Suzuki A, Hajarnis S, Ma Z, Chapin HC, Caplan MJ, Pontoglio M, Somlo S, Igarashi P (2011) Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proc Natl Acad Sci USA 108:10679-10684
107. Gresh L, Fischer E, Reimann A, Tanguy M, Garbay S, Shao X, Hiesberger T, Fiette L, Igarashi P, Yaniv M, Pontoglio M (2004) A transcriptional network in polycystic kidney disease. EMBO J 23:1657-1668
108. Wang X, Harris PC, Somlo S, Batlle D, Torres VE (2009) Effect of calcium-sensing receptor activation in models of autosomal recessive or dominant polycystic kidney disease. Nephrol Dial Transplant 24:526-534
109. Lefkimmiatis K, Srikanthan M, Maiellaro I, Moyer MP, Curci S, Hofer AM (2009) Store-operated cyclic AMP signalling mediated by STIM1. Nat Cell Biol 11:433-442
110. Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M (2012) Altered store operated calcium entry increases cyclic 3′,5′-adenosine monophosphate production and extracellular signal-regulated kinases 1 and 2 phosphorylation in polycystin-2-defective cholangiocytes. Hepatology 55:856-868
111. Yamaguchi T, Pelling JC, Ramaswamy NT, Eppler JW, Wallace DP, Nagao S, Rome LA, Sullivan LP, Grantham JJ (2000) cAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway. Kidney Int 57:1460-1471
112. Yamaguchi T, Nagao S, Wallace DP, Belibi FA, Cowley BD, Pelling JC, Grantham JJ (2003) Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys. Kidney Int 63:1983-1994
113. Cowley BD Jr (2008) Calcium, cyclic AMP, and MAP kinases: dysregulation in polycystic kidney disease. Kidney Int 73:251-253
114. Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, Calvet JP (2004) Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J Biol Chem 279:40419-40430
115. Yamaguchi T, Hempson SJ, Reif GA, Hedge AM, Wallace DP (2006) Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol 17:178-187
116. Nagao S, Nishii K, Yoshihara D, Kurahashi H, Nagaoka K, Yamashita T, Takahashi H, Yamaguchi T, Calvet JP, Wallace DP (2008) Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+rat. Kidney Int 73:269-277
117. 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
118. 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
119. 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
120. Lieberthal W, Levine JS (2012) Mammalian target of rapamycin and the kidney part I: the signaling pathway. Am J Physiol Renal Physiol 303:F1-F10
121. Lieberthal W, Levine JS (2012) Mammalian target of rapamycin and the kidney part II: pathophysiology and therapeutic implications. Am J Physiol Renal Physiol 303:F180-F191
122. Boletta A (2009) Emerging evidence of a link between the polycystins and the mTOR pathways. Pathogenetics 2:6
123. Lieberthal W, Levine JS (2009) The role of the mammalian target of rapamycin (mTOR) in renal disease. J Am Soc Nephrol 20:2493-2502
124. Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek KB, Germino GG, Pandolfi PP, Boletta A (2009) Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6 K and 4EBP1. Mol Cell Biol 29:2359-2371
125. Shibazaki S, Yu Z, Nishio S, Tian X, Thomson RB, Mitobe M, Louvi A, Velazquez H, Ishibe S, Cantley LG, Igarashi P, Somlo S (2008) Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1. Hum Mol Genet 17:1505-1516
126. Ballif BA, Roux PP, Gerber SA, MacKeigan JP, Blenis J, Gygi SP (2005) Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci USA 102:667-672
127. Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Godel M, Muller K, Herbst M, Hornung M, Doerken M, Kottgen 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
128. Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R, Mathiasen IS, Jaattela M (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 25:193-205
129. Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ (2011) Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci USA 108:2462-2467
130. Kim E, Arnould T, Sellin LK, Benzing T, Fan MJ, Gruning W, Sokol SY, Drummond I, Walz G (1999) The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 274:4947-4953
131. Habas R, Dawid IB (2005) Dishevelled and Wnt signaling: is the nucleus the final frontier? J Biol 4:2
132. Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G (2005) Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 37:537-543
133. Saadi-Kheddouci S, Berrebi D, Romagnolo B, Cluzeaud F, Peuchmaur M, Kahn A, Vandewalle A, Perret C (2001) Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene. Oncogene 20:5972-5981
134. Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ (2008) Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling. Hum Mol Genet 17:3105-3117
135. Happe H, Leonhard WN, van der Wal A, van de Water B, Lantinga-van Leeuwen IS, Breuning MH, de Heer E, Peters DJ (2009) Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Hum Mol Genet 18:2532-2542
136. Romaker D, Puetz M, Teschner S, Donauer J, Geyer M, Gerke P, Rumberger B, Dworniczak B, Pennekamp P, Buchholz B, Neumann HP, Kumar R, Gloy J, Eckardt KU, Walz G (2009) Increased expression of secreted frizzled-related protein 4 in polycystic kidneys. J Am Soc Nephrol 20:48-56
137. Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C,
138. Boca M, D'Amato L, Distefano G, Polishchuk RS, Germino GG, Boletta A (2007) Polycystin-1 induces cell migration by regulating phosphatidylinositol 3-kinase-dependent cytoskeletal rearrangements and GSK3beta-dependent cell-cell mechanical adhesion. Mol Biol Cell 18:4050-4061
139. Woo D (1995) Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 333:18-25
140. Lanoix J, D'Agati V, Szabolcs M, Trudel M (1996) Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). Oncogene 13:1153-1160
141. Zhou XJ, Kukes G (1998) Pathogenesis of autosomal dominant polycystic kidney disease: role of apoptosis. Diagn Mol Pathol 7:65-68
142. Wilson PD (2004) Polycystic kidney disease. N Engl J Med 350:151-164
143. Ecder T, Melnikov VY, Stanley M, Korular D, Lucia MS, Schrier RW, Edelstein CL (2002) Caspases, Bcl-2 proteins and apoptosis in autosomal-dominant polycystic kidney disease. Kidney Int 61:1220-1230
144. Edelstein CL (2005) What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)? Cell Cycle 4:1550-1554
145. Goilav B, Satlin LM, Wilson PD (2008) Pathways of apoptosis in human autosomal recessive and autosomal dominant polycystic kidney diseases. Pediatr Nephrol 23:1473-1482
146. Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG (2002) PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 109:157-168
147. Park JY, 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
148. Bukanov NO, Smith LA, Klinger KW, Ledbetter SR, Ibraghimov-Beskrovnaya O (2006) Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature 444:949-952
149. Park JY, Park SH, Weiss RH (2009) Disparate effects of roscovitine on renal tubular epithelial cell apoptosis and senescence: implications for autosomal dominant polycystic kidney disease. Am J Nephrol 29:509-515
150. Trudel M, D'Agati V (1992) A model of polycystic kidney disease in SBM transgenic mice. Contrib Nephrol 97:47-59
151. Trudel M, Lanoix J, Barisoni L, Blouin MJ, Desforges M, L'Italien C, D'Agati V (1997) C-myc-induced apoptosis in polycystic kidney disease is Bcl-2 and p53 independent. J Exp Med 186:1873-1884
152. Schafer K, Gretz N, Bader M, Oberbaumer I, Eckardt KU, Kriz W, Bachmann S (1994) Characterization of the Han: SPRD rat model for hereditary polycystic kidney disease. Kidney Int 46:134-152
153. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229-240
154. -/- mouse. Am J Physiol 271:F184-F193
155. Bouillet P, Robati M, Bath M, Strasser A (2005) Polycystic kidney disease prevented by transgenic RNA interference. Cell Death Differ 12:831-833
156. Hughes P, Robati M, Lu W, Zhou J, Strasser A, Bouillet P (2006) Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms. Cell Death Differ 13:1123-1127
157. Moser M, Pscherer A, Roth C, Becker J, Mucher G, Zerres K, Dixkens C, Weis J, Guay-Woodford L, Buettner R, Fassler R (1997) Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta. Genes Dev 11:1938-1948
158. Tao Y, Kim J, Faubel S, Wu JC, Falk SA, Schrier RW, Edelstein CL (2005) Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proc Natl Acad Sci USA 102:6954-6959
159. Tao Y, Kim J, Stanley M, He Z, Faubel S, Schrier RW, Edelstein CL (2005) Pathways of caspase-mediated apoptosis in autosomal-dominant polycystic kidney disease (ADPKD). Kidney Int 67:909-919
160. Edelstein CL (2008) Mammalian target of rapamycin and caspase inhibitors in polycystic kidney disease. Clin J Am Soc Nephrol 3:1219-1226
161. Tao Y, Zafar I, Kim J, Schrier RW, Edelstein CL (2008) Caspase-3 gene deletion prolongs survival in polycystic kidney disease. J Am Soc Nephrol 19:749-755
162. Trudel M, Barisoni L, Lanoix J, D'Agati V (1998) Polycystic kidney disease in SBM transgenic mice: role of c-myc in disease induction and progression. Am J Pathol 152:219-229
163. Trudel M, D'Agati V, Costantini F (1991) C-myc as an inducer of polycystic kidney disease in transgenic mice. Kidney Int 39:665-671
164. Ricker JL, Mata JE, Iversen PL, Gattone VH (2002) c-myc antisense oligonucleotide treatment ameliorates murine ARPKD. Kidney Int 61:S125-S131
165. Goilav B (2011) Apoptosis in polycystic kidney disease. Biochim Biophys Acta 1812:1272-1280
166. 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
167. Park EY, Sung YH, Yang MH, Noh JY, Park SY, Lee TY, Yook YJ, Yoo KH, Roh KJ, Kim I, Hwang YH, Oh GT, Seong JK, Ahn C, Lee HW, Park JH (2009) Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice. J Biol Chem 284:7214-7222
168. i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype. Circ Res 96:873-880
169. 2+ release and apoptosis. Proc Natl Acad Sci USA 105:2427-2432
170. 3 receptor-mitochondria connection in apoptosis and autophagy. Biochim Biophys Acta 1813:1003-1013
171. Zheng R, Zhang Z, Lv X, Fan J, Chen Y, Wang Y, Tan R, Liu Y, Zhou Q (2008) Polycystin-1 induced apoptosis and cell cycle arrest in G0/G1 phase in cancer cells. Cell Biol Int 32:427-435
172. Winyard PJ, Nauta J, Lirenman DS, Hardman P, Sams VR, Risdon RA, Woolf AS (1996) Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int 49:135-146