Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation

Human Molecular Genetics

Volumn 22, Issue 10, 2013, Pages 1924-1939

  Streets, Andrew J ^a   Wessely, Oliver ^b   Peters, Dorien J M ^c   Ong, Albert C M ^a  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b LERNER RESEARCH INSTITUTE   (United States)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM ION; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIC AMP DEPENDENT PROTEIN KINASE ANCHORING PROTEIN; PHOSPHOPROTEIN PHOSPHATASE 1; POLYCYSTIN 1; POLYCYSTIN 2; SMALL INTERFERING RNA;

AMINO ACID SEQUENCE; ANTIBODY SPECIFICITY; ARTICLE; CELL PROLIFERATION; DIMERIZATION; EMBRYO; GENETIC CONSERVATION; GROWTH INHIBITION; HETEROLOGOUS EXPRESSION; IN VITRO STUDY; MDCK CELL; MISSENSE MUTATION; MITOSIS SPINDLE; MOLECULAR RECOGNITION; NONHUMAN; PHENOTYPE; POINT MUTATION; PRIORITY JOURNAL; PRONEPHROS; PROTEIN CONFORMATION; PROTEIN DEPHOSPHORYLATION; PROTEIN HYPERPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; STABLE EXPRESSION; XENOPUS;

ANIMALS; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; DOGS; HEK293 CELLS; HELA CELLS; HUMANS; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICE, KNOCKOUT; MUTATION; PHOSPHORYLATION; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; PROTEIN PHOSPHATASE 1; PROTEIN STRUCTURE, TERTIARY; TRPP CATION CHANNELS; XENOPUS LAEVIS;

EID: 84877056647     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddt031     Document Type: Article

References (60)

1. Torres, V.E., Harris, P.C. and Pirson, Y. (2007) Autosomal dominant polycystic kidney disease. Lancet, 369, 1287-1301.
2. Ong, A.C. and Harris, P.C. (2005) Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int., 67, 1234-1247.
3. Newby, L.J., Streets, A.J., Zhao, Y., Harris, P.C., Ward, C.J. and Ong, A.C. (2002) Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J. Biol. Chem., 277, 20763-20773.
4. Giamarchi, A., Feng, S., Rodat-Despoix, L., Xu, Y., Bubenshchikova, E., Newby, L.J., Hao, J., Gaudioso, C., Crest, M., Lupas, A.N. et al. (2010) A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes. EMBO J., 29, 1176-1191.
5. Yu, Y., Ulbrich, M.H., Li, M.H., Buraei, Z., Chen, X.Z., Ong, A.C., Tong, L., Isacoff, E.Y. and Yang, J. (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc. Natl Acad. Sci. USA, 106, 11558-11563.
6. Feng, S., Rodat-Despoix, L., Delmas, P. and Ong, A.C. (2011) A single amino acid residue constitutes the third dimerization domain essential for the assembly and function of the tetrameric polycystin-2 (TRPP2) channel. J. Biol. Chem., 286, 18994-19000.
7. Feng, S., Okenka, G.M., Bai, C.X., Streets, A.J., Newby, L.J., DeChant, B.T., Tsiokas, L., Obara, T. and Ong, A.C. (2008) Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2. J. Biol. Chem., 283, 28471-28479.
8. Ong, A.C. (2000) Polycystin expression in the kidney and other tissues: complexity, consensus and controversy. Exp. Nephrol., 8, 208-214.
9. 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. et al. (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet., 33, 129-137.
10. Rundle, D.R., Gorbsky, G. and 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.
11. Jurczyk, A., Gromley, A., Redick, S., San Agustin, J., Witman, G., Pazour, G.J., Peters, D.J. and 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.
12. Bhunia, A.K., Piontek, K., Boletta, A., Liu, L., Qian, F., Xu, P.N., Germino, F.J. and Germino, G.G. (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.
13. Li, X., Luo, Y., Starremans, P.G., McNamara, C.A., Pei, Y. and 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.
14. Streets, A.J., Newby, L.J., O'Hare, M.J., Bukanov, N.O., Ibraghimov-Beskrovnaya, O. and Ong, A.C. (2003) Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesion. J. Am. Soc. Nephrol., 14, 1804-1815.
15. Ibraghimov-Beskrovnaya, O., Bukanov, N.O., Donohue, L.C., Dackowski, W.R., Klinger, K.W. and Landes, G.M. (2000) Strong homophilic interactions of the Ig-like domains of polycystin-1, the protein product of an autosomal dominant polycystic kidney disease gene, PKD1. Hum. Mol. Genet., 9, 1641-1649.
16. Streets, A.J., Wagner, B.E., Harris, P.C., Ward, C.J. and Ong, A.C. (2009) Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J. Cell Sci., 122, 1410-1417.
17. Li, Y., Santoso, N.G., Yu, S., Woodward, O.M., Qian, F. and Guggino, W.B. (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.
18. Mekahli, D., Sammels, E., Luyten, T., Welkenhuyzen, K., van den Heuvel, L.P., Levtchenko, E.N., Gijsbers, R., Bultynck, G., Parys, J.B., De Smedt, H. et al. (2012) Polycystin-1 and polycystin-2 are both required to amplify inositol-trisphosphate-induced Ca2+ release. Cell Calcium, 51, 452-458.
19. Hogan, M.C., Manganelli, L., Woollard, J.R., Masyuk, A.I., Masyuk, T.V., Tammachote, R., Huang, B.Q., Leontovich, A.A., Beito, T.G., Madden, B.J. et al. (2009) Characterization of PKD protein-positive exosome-like vesicles. J. Am. Soc. Nephrol., 20, 278-288.
20. Plotnikova, O.V., Pugacheva, E.N. and Golemis, E.A. (2011) Aurora A kinase activity influences calcium signaling in kidney cells. J. Cell. Biol., 193, 1021-1032.
21. Kottgen, M., Benzing, T., Simmen, T., Tauber, R., Buchholz, B., Feliciangeli, S., Huber, T.B., Schermer, B., Kramer-Zucker, A., Hopker, K. et al. (2005) Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J., 24, 705-716.
22. Streets, A.J., Moon, D.J., Kane, M.E., Obara, T. and Ong, A.C. (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.
23. Parker, E., Newby, L.J., Sharpe, C.C., Rossetti, S., Streets, A.J., Harris, P.C., O'Hare, M.J. and Ong, A.C. (2007) Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int., 72, 157-165.
24. Novalic, Z., van der Wal, A.M., Leonhard, W.N., Koehl, G., Breuning, M.H., Geissler, E.K., de Heer, E. and Peters, D.J. (2012) Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. J. Am. Soc. Nephrol., 23, 842-853.
25. Mitsuhashi, S., Matsuura, N., Ubukata, M., Oikawa, H., Shima, H. and Kikuchi, K. (2001) Tautomycetin is a novel and specific inhibitor of serine/threonine protein phosphatase type 1, PP1. Biochem. Biophys. Res. Commun., 287, 328-331.
26. Favre, B., Turowski, P. and Hemmings, B.A. (1997) Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin. J. Biol. Chem., 272, 13856-13863.
27. Cohen, P.T. (2002) Protein phosphatase 1-targeted in many directions. J. Cell. Sci., 115, 241-256.
28. Schillace, R.V. and Scott, J.D. (1999) Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220. Curr. Biol., 9, 321-324.
29. Schillace, R.V. and Scott, J.D. (1999) Organization of kinases, phosphatases, and receptor signaling complexes. J. Clin. Invest., 103, 761-765.
30. Tan, Y.C., Blumenfeld, J.D., Anghel, R., Donahue, S., Belenkaya, R., Balina, M., Parker, T., Levine, D., Leonard, D.G. and Rennert, H. (2009) Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease. Hum. Mutat., 30, 264-273.
31. Parnell, S.C., Puri, S., Wallace, D.P. and Calvet, J.P. (2012) Protein phosphatase-1alpha interacts with and dephosphorylates polycystin-1. PloS One, 7, e36798.
32. Sammels, E., Devogelaere, B., Mekahli, D., Bultynck, G., Missiaen, L., Parys, J.B., Cai, Y., Somlo, S. and De Smedt, H. (2010) Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J. Biol. Chem., 285, 18794-18805.
33. Streets, A.J., Needham, A.J., Gill, S.K. and Ong, A.C. (2010) Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity. Mol. Biol. Cell, 21, 3853-3865.
34. Grimm, D.H., Karihaloo, A., Cai, Y., Somlo, S., Cantley, L.G. and Caplan, M.J. (2006) Polycystin-2 regulates proliferation and branching morphogenesis in kidney epithelial cells. J. Biol. Chem., 281, 137-144.
35. Liang, G., Li, Q., Tang, Y., Kokame, K., Kikuchi, T., Wu, G. and Chen, X.Z. (2008) Polycystin-2 is regulated by endoplasmic reticulum-associated degradation. Hum Mol Genet, 17, 1109-1119.
36. Fan, L.X., Li, X., Magenheimer, B. and Calvet, J.P. (2012) Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int., 81, 76-85.
37. Kim, H., Bae, Y., Jeong, W., Ahn, C. and Kang, S. (2004) Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/ S-phase transition. Eur. J. Hum. Genet., 12, 433-440.
38. Tran, U., Zakin, L., Schweickert, A., Agrawal, R., Doger, R., Blum, M., De Robertis, E.M. and Wessely, O. (2010) The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development, 137, 1107-1116.
39. Tran, U., Pickney, L.M., Ozpolat, B.D. and Wessely, O. (2007) Xenopus Bicaudal-C is required for the differentiation of the amphibian pronephros. Dev. Biol., 307, 152-164.
40. Yu, Y., Yoon, S.O., Poulogiannis, G., Yang, Q., Ma, X.M., Villen, J., Kubica, N., Hoffman, G.R., Cantley, L.C., Gygi, S.P. et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science, 332, 1322-1326.
41. Hsu, P.P., Kang, S.A., Rameseder, J., Zhang, Y., Ottina, K.A., Lim, D., Peterson, T.R., Choi, Y., Gray, N.S., Yaffe, M.B. et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science, 332, 1317-1322.
42. Huttlin, E.L., Jedrychowski, M.P., Elias, J.E., Goswami, T., Rad, R., Beausoleil, S.A., Villen, J., Haas, W., Sowa, M.E. and Gygi, S.P. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell, 143, 1174-1189.
43. Molina, H., Horn, D.M., Tang, N., Mathivanan, S. and Pandey, A. (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc. Natl. Acad. Sci. USA, 104, 2199-2204.
44. Olsen, J.V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P. and Mann, M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell, 127, 635-648.
45. Hoffert, J.D., Pisitkun, T., Wang, G., Shen, R.-F. and Knepper, M.A. (2006) Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc. Natl. Acad. Sci. USA, 103, 7159-7164.
46. Zanivan, S., Gnad, F., Wickstrom, S.A., Geiger, T., Macek, B., Cox, J., Fassler, R. and Mann, M. (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J. Proteome. Res., 7, 5314-5326.
47. Li, H., Xing, X., Ding, G., Li, Q., Wang, C., Xie, L., Zeng, R. and Li, Y. (2009) SysPTM: a systematic resource for proteomic research on posttranslational modifications. Mol. Cell. Proteomics., 8, 1839-1849.
48. Cai, Y., Anyatonwu, G., Okuhara, D., Lee, K.B., Yu, Z., Onoe, T., Mei, C.L., Qian, Q., Geng, L., Wiztgall, R. et al. (2004) Calcium dependence of polycystin-2 channel activity is modulated by phosphorylation at Ser812. J. Biol. Chem., 279, 19987-19995.
49. Torres, V.E. (2004) Cyclic AMP, at the hub of the cystic cycle. Kidney Int., 66, 1283-1285.
50. Choi, Y.H., Suzuki, A., Hajarnis, S., Ma, Z., Chapin, H.C., Caplan, M.J., Pontoglio, M., Somlo, S. and 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.
51. Hendrickx, A., Beullens, M., Ceulemans, H., Den Abt, T., Van Eynde, A., Nicolaescu, E., Lesage, B. and Bollen, M. (2009) Docking motif-guided mapping of the interactome of protein phosphatase-1.Chem.Biol., 16, 365-371.
52. 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. (2003) Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells. Hum. Mol. Genet., 12, 1875-1880.
53. Bai, C.X., Kim, S., Li, W.P., Streets, A.J., Ong, A.C. and Tsiokas, L. (2008) Activation of TRPP2 through mDia1-dependent voltage gating. EMBO J, 27, 1345-1356.
54. Parry, H., McDougall, A. and Whitaker, M. (2005) Microdomains bounded by endoplasmic reticulum segregate cell cycle calcium transients in syncytial Drosophila embryos. J. Cell Biol., 171, 47-59.
55. Ong, A.C., Ward, C.J., Butler, R.J., Biddolph, S., Bowker, C., Torra, R., Pei, Y. and Harris, P.C. (1999) Coordinate expression of the autosomal dominant polycystic kidney disease proteins, polycystin-2 and polycystin-1, in normal and cystic tissue. Am. J. Pathol., 154, 1721-1729.
56. Vergarajauregui, S. and Puertollano, R. (2006) Two di-leucine motifs regulate trafficking of mucolipin-1 to lysosomes. Traffic, 7, 337-353.
57. Frohlich, O., Klein, J.D., Smith, P.M., Sands, J.M. and Gunn, R.B. (2004) Urea transport in MDCK cells that are stably transfected with UT-A1. Am. J. Physiol. Cell Physiol., 286, C1264-1270.
58. Ong, A.C., Harris, P.C., Davies, D.R., Pritchard, L., Rossetti, S., Biddolph, S., Vaux, D.J., Migone, N. and Ward, C.J. (1999) Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue. Kidney Int., 56, 1324-1333.
59. Sive, H.L., Grainger, R.M. and Harland, R.M. (2000) Early Development of Xenopus laevis: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
60. Nieuwkoop, P.D. and Faber, J. (1994) Normal Table of Xenopus laevis. Garland Publishing, New York.