Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Polycystin-2

  • Daryl L. Goad
  • Michael A. Grillo
  • Peter Koulen
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_345

Synonyms

 APKD2;  PC2;  PKD2;  PKD4;  TRPP1

Historical Background

The pkd2 gene encodes the protein polycystin-2, a member of the transient receptor potential (TRP) protein family. The genetic locus for pkd2 was elucidated in 1993 by the Kumar and Spruit groups during the search for genes involved in autosomal dominant polycystic kidney disease (ADPKD) (Kimberling et al. 1993; Peters et al. 1993). Mutations in pkd2 account for approximately 15% of the ADPKD patients, with the remainder of ADPKD patients having mutations in pkd1 or pkhd1 (Koulen and McClung 2006). Mutations in pkd2 may also contribute to inadequate heart function, a leading cause of mortality in ADPKD patients, as observed in patients, in pkd2+/− mice that lack renal deficiency, but display an age-dependent increase in cardiac dysfunction, and in pdk2+/− zebra fish, which exhibit impaired cardiac output (Chapman et al. 2010; Kuo et al. 2014, 2016; Paavola et al. 2013).

Functionally, polycystin-2 has been implicated in...

This is a preview of subscription content, log in to check access.

References

  1. AbouAlaiwi WA, Takahashi M, Mell BR, Jones TJ, Ratnam S, Kolb RJ, et al. Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res. 2009;104(7):860–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Allen MD, Qamar S, Vadivelu MK, Sandford RN, Bycroft M. A high-resolution structure of the EF-hand domain of human polycystin-2. Protein Sci. 2014;23(9):1301–8.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anyatonwu GI, Estrada M, Tian X, Somlo S, Ehrlich BE. Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc Natl Acad Sci USA. 2007;104(15):6454–9.CrossRefGoogle Scholar
  4. Barr MM, Sternberg PW. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature. 1999;401(6751):386–9.PubMedGoogle Scholar
  5. Cai Y, Maeda Y, Cedzich A, Torres VE, Wu G, Hayashi T, Mochizuki T, Park JH, Witzgall R, Somlo S. Identification and characterization of polycystin-2, the PKD2 gene product. J Biol Chem. 1999;274(40):28557–65.CrossRefPubMedGoogle Scholar
  6. Chapin HC, Caplan MJ. The cell biology of polycystic kidney disease. J Cell Biol. 2010;191(4):701–10.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Chapman AB, Stepniakowski K, Rahbari-Oskoui F. Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):153–63.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Gallagher AR, Germino GG, Somio S. Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):118–30.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Gao H, Wang Y, Wegierski T, Skouloudaki K, Putz M, Fu X, et al. PRKCSH/80 K-H, the protein mutated in polycystic liver disease, protects polycystin-2/TRPP2 against HERP-mediated degradation. Hum Mol Genet. 2010;19(1):16–24.CrossRefPubMedGoogle Scholar
  10. Geng L, Okuhara D, Yu Z, Tian X, Cai Y, Shibazaki S, et al. Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. J Cell Sci. 2006;119(Pt 7):1383–95.CrossRefPubMedGoogle Scholar
  11. Hogan MC, Manganelli L, Woolard JR, Masyuk AI, Masyuk TV, Tammachote R, et al. Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol. 2009;20(2):278–88.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Kaja S, Hilgenberg JD, Rybalchenko V, Medina-Ortiz WE, Gregg EV, Koulen P. Polycystin-2 expression and function in adult mouse lacrimal acinar cells. Invest Ophthalmol Vis Sci. 2011;52(8):5605–11.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993;18(3):467–72.CrossRefPubMedGoogle Scholar
  14. 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. Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J. 2005;24:705–16.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Koulen P, McClung NM. Polycystin 2. [Web Page]: Nature Molecule Pages; 2006 [cited 2006 May].Google Scholar
  16. Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S. Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol. 2002;4(3):191–7.CrossRefPubMedGoogle Scholar
  17. Koulen P, Duncan RS, Liu J, Cohen NE, Yannazzo JA, McClung N, Lockhart CL, Branden M, Buechner M. Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans. Cell Calcium. 2005;37(6):593–601 .Epub 2005 Apr 14CrossRefPubMedGoogle Scholar
  18. Kuo IY, Kwaczala AT, Nguyen L, Russell KS, Campbell SG, Ehrlich BE. Decreased polycystin 2 expression alters calcium-contraction coupling and changes β-adrenergic signaling pathways. PNAS. 2014;111(46):16604–9.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Kuo IY, Duong SL, Nguyen L, Ehrlich BE. Decreased polycystin 2 levels result in non-renal cardiac dysfunction with aging. PLoS ONE. 2016;11(4):e0153632.Epub 2016 Apr 15PubMedPubMedCentralCrossRefGoogle Scholar
  20. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol. 2005;7(12):1202–12.CrossRefPubMedGoogle Scholar
  21. Miyagi K, Kiyonaka S, Yamada K, Miki T, Mori E, Kato K, et al. A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca 2+ entry via association with TRPC3 and TRPC7. J Biol Chem. 2009;284(49):34400–12.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Montalbetti N, Li Q, Wu Y, Chen XZ, Cantiello HF. Polycystin-2 cation channel function in the human syncytiotrophoblast is regulated by microtubular structures. J Physiol. 2007;579(Pt 3):717–28.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Peters DJM, Spruit L, Saris JJ, Ravine D, Sandkuijl LA, Fossdal R, et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet. 1993;5(4):359–62.CrossRefPubMedGoogle Scholar
  24. Petri ET, Celic A, Kennedy SD, Ehrlich BE, Boggon TJ, Hodsdon ME. 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 U S A. 2010;107(20):9176–81.Google Scholar
  25. Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, et al. Polycystin-2 activation by inositol 1, 4, 5-trisphosphate-induced Ca 2+ release requires its direct association with the inositol 1, 4, 5-trisphosphate receptor in a signaling microdomain. J Biol Chem. 2010;285(24):18794–805.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell. 2009;139(3):587–96.CrossRefPubMedGoogle Scholar
  27. Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, et al. Mammalian target of rapamycin regulates vascular endothelial growth factor-dependent liver cyst growth in polycystin-2-defective mice. Hepatology. 2010;51(5):1778–88.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Tsiokas L. Function and regulation of TRPP2 at the plasma membrane. Am J Physiol Ren Physiol. 2009;297(1):F1–9.CrossRefGoogle Scholar
  29. Tsiokas L, Kim S, Ong EC. Cell biology of polycystin-2. Cell Signal. 2007;19(3):444–53.CrossRefPubMedGoogle Scholar
  30. Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 2010;137(7):1075–84.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Xiao ZS, Quarles LD. Role of the polycytin-primary cilia complex in bone development and mechanosensing. Ann N Y Acad Sci. 2010;1192(1):410–21.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol. 2009;71:83–113.CrossRefPubMedGoogle Scholar
  33. Paavola J, Schliffke S, Rossetti S, Kuo IY, Yuan S, Sun Z, Harris PC, Torres VE, Ehrlich BE. Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. J Mol Cell Cardiol. 2013;58:199–208.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Daryl L. Goad
    • 1
  • Michael A. Grillo
    • 2
  • Peter Koulen
    • 2
  1. 1.Department of Natural Science, Social Science, and MathematicsHutchinson Community CollegeHutchinsonUSA
  2. 2.Department of Ophthalmology and Department of Basic Medical ScienceUniversity of Missouri - Kansas City School of Medicine, Vision Research CenterKansas CityUSA