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Encyclopedia of Signaling Molecules pp 4106–4110Cite as

Polycystin-2

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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 Ca 2+...

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References

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Barr MM, Sternberg PW. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature. 1999;401(6751):386–9.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Chapin HC, Caplan MJ. The cell biology of polycystic kidney disease. J Cell Biol. 2010;191(4):701–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chapman AB, Stepniakowski K, Rahbari-Oskoui F. Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):153–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gallagher AR, Germino GG, Somio S. Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):118–30.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koulen P, McClung NM. Polycystin 2. [Web Page]: Nature Molecule Pages; 2006 [cited 2006 May].

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 14

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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 15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Tsiokas L. Function and regulation of TRPP2 at the plasma membrane. Am J Physiol Ren Physiol. 2009;297(1):F1–9.

    Article  CAS  Google Scholar 

  • Tsiokas L, Kim S, Ong EC. Cell biology of polycystin-2. Cell Signal. 2007;19(3):444–53.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol. 2009;71:83–113.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Natural Science, Social Science, and Mathematics, Hutchinson Community College, 1300 N. Plum Ave, Hutchinson, KS, 67501, USA

    Daryl L. Goad

  2. Department of Ophthalmology and Department of Basic Medical Science, University of Missouri - Kansas City School of Medicine, Vision Research Center, 2411 Holmes Street, Kansas City, MO, 64108, USA

    Michael A. Grillo & Peter Koulen

Authors
  1. Daryl L. Goad
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  2. Michael A. Grillo
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  3. Peter Koulen
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Corresponding author

Correspondence to Peter Koulen .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Goad, D.L., Grillo, M.A., Koulen, P. (2018). Polycystin-2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_345

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