Skip to main content

Advertisement

SpringerLink
Log in

Polycystin-1 cleavage and the regulation of transcriptional pathways

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage renal disease, affecting approximately 1 in 1,000 people. The disease is characterized by the development of numerous large fluid-filled renal cysts over the course of decades. These cysts compress the surrounding renal parenchyma and impair its function. Mutations in two genes are responsible for ADPKD. The protein products of both of these genes, polycystin-1 and polycystin-2, localize to the primary cilium and participate in a wide variety of signaling pathways. Polycystin-1 undergoes several proteolytic cleavages that produce fragments which manifest biological activities. Recent results suggest that the production of polycystin-1 cleavage fragments is necessary and sufficient to account for at least some, although certainly not all, of the physiological functions of the parent protein.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Calvet JP, Grantham JJ (2001) The genetics and physiology of polycystic kidney disease. Semin Nephrol 21:107–123

    Article  CAS  PubMed  Google Scholar 

  2. Takiar V, Caplan MJ (2011) Polycystic kidney disease: pathogenesis and potential therapies. Biochim Biophys Acta 1812:1337–4133

    Google Scholar 

  3. Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321–337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Gabow PA (1993) Autosomal dominant polycystic kidney disease. N Engl J Med 329:332–342

    Article  CAS  PubMed  Google Scholar 

  5. Qian F, Watnick TJ, Onuchic LF, Germino GG (1996) The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 87:979–987

    Article  CAS  PubMed  Google Scholar 

  6. Bastos AP, Piontek K, Silva AM, Martini D, Menezes LF, Fonseca JM, Fonseca II, Germino GG, Onuchic LF (2009) Pkd1 haploinsufficiency increases renal damage and induces microcyst formation following ischemia/reperfusion. J Am Soc Nephrol 20:2389–2402

    Article  CAS  PubMed  Google Scholar 

  7. Takakura A, Contrino L, Zhou X, Bonventre JV, Sun Y, Humphreys BD, Zhou J (2009) Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum Mol Genet 18:2523–2531

    Article  CAS  PubMed  Google Scholar 

  8. Harris PC, Germino G, Klinger K, Landes G, van Adelsberg J (1995) The PKD1 gene product. Nat Med 1:493

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Article  CAS  PubMed  Google Scholar 

  10. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millan JL, Gamble V, Harris PC (1995) The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet 10:151–160

    Article  CAS  PubMed  Google Scholar 

  11. Lohning C, Pohlschmidt M, Glucksmann-Kuis MA, Duyk G, Bork P, Schneider MO, Reeders ST, Frischauf AM (1996) Structural motifs of the PKD1 protein. Nephrol Dial Transplant 11[Suppl 6]:2–4

    Article  CAS  PubMed  Google Scholar 

  12. Ibraghimov-Beskrovnaya O, Bukanov NO, Donohue LC, Dackowski WR, Klinger KW, Landes GM (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

    Article  CAS  PubMed  Google Scholar 

  13. Streets AJ, Newby LJ, O’Hare MJ, Bukanov NO, Ibraghimov-Beskrovnaya O, Ong AC (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

    Article  CAS  PubMed  Google Scholar 

  14. Streets AJ, Wagner BE, Harris PC, Ward CJ, Ong AC (2009) Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J Cell Sci 122:1410–1417

    Article  CAS  PubMed  Google Scholar 

  15. Babich V, Zeng WZ, Yeh BI, Ibraghimov-Beskrovnaya O, Cai Y, Somlo S, Huang CL (2004) The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. J Biol Chem 279:25582–25589

    Article  CAS  PubMed  Google Scholar 

  16. van Adelsberg J (1999) Peptides from the PKD repeats of polycystin, the PKD1 gene product, modulate pattern formation in the developing kidney. Dev Genet 24:299–308

    Article  PubMed  Google Scholar 

  17. Patel A, Honore E (2010) Polycystins and renovascular mechanosensory transduction. Nat Rev Nephrol 6:530–538

    Google Scholar 

  18. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kawaguchi H, Yamanaka A, Uchida K, Shibasaki K, Sokabe T, Maruyama Y, Yanagawa Y, Murakami S, Tominaga M (2010) Activation of polycystic kidney disease-2-like 1 (PKD2L1)-PKD1L3 complex by acid in mouse taste cells. J Biol Chem 285:17277–17281

    Article  CAS  PubMed  Google Scholar 

  20. Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 103:12569–12574

    Article  CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed  Google Scholar 

  23. Le NH, van der Bent P, Huls G, van de Wetering M, Loghman-Adham M, Ong AC, Calvet JP, Clevers H, Breuning MH, van Dam H, Peters DJ (2004) Aberrant polycystin-1 expression results in modification of activator protein-1 activity, whereas Wnt signaling remains unaffected. J Biol Chem 279:27472–27481

    Article  CAS  PubMed  Google Scholar 

  24. Parnell SC, Magenheimer BS, Maser RL, Zien CA, Frischauf AM, Calvet JP (2002) Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins. J Biol Chem 277:19566–19572

    Article  CAS  PubMed  Google Scholar 

  25. Kim E, Arnould T, Sellin L, Benzing T, Comella N, Kocher O, Tsiokas L, Sukhatme VP, Walz G (1999) Interaction between RGS7 and polycystin. Proc Natl Acad Sci USA 96:6371–6376

    Article  CAS  PubMed  Google Scholar 

  26. Arnould T, Kim E, Tsiokas L, Jochimsen F, Gruning W, Chang JD, Walz G (1998) The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1. J Biol Chem 273:6013–6018

    Article  CAS  PubMed  Google Scholar 

  27. 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

    Article  CAS  PubMed  Google Scholar 

  28. Talbot JJ, Shillingford JM, Vasanth S, Doerr N, Mukherjee S, Kinter MT, Watnick T, Weimbs T (2011) Polycystin-1 regulates STAT activity by a dual mechanism. Proc Natl Acad Sci USA 108:7985–7990

    Article  CAS  PubMed  Google Scholar 

  29. Boletta A, Qian F, Onuchic LF, Bhunia AK, Phakdeekitcharoen B, Hanaoka K, Guggino W, Monaco L, Germino GG (2000) Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol Cell 6:1267–1273

    Article  CAS  PubMed  Google Scholar 

  30. Sutters M, Yamaguchi T, Maser RL, Magenheimer BS, St John PL, Abrahamson DR, Grantham JJ, Calvet JP (2001) Polycystin-1 transforms the cAMP growth-responsive phenotype of —1 cells. Kidney Int 60:484–494

    Article  CAS  PubMed  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. Gonzalez-Perrett S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, Harris PC, Reisin IL, Arnaout MA, Cantiello HF (2001) Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. Proc Natl Acad Sci USA 98:1182–1187

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. 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

    Article  CAS  PubMed  Google Scholar 

  37. 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

    Article  CAS  PubMed  Google Scholar 

  38. 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

    Article  CAS  PubMed  Google Scholar 

  39. Delmas P, Nomura H, Li X, Lakkis M, Luo Y, Segal Y, Fernandez-Fernandez JM, Harris P, Frischauf AM, Brown DA, Zhou J (2002) Constitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2. J Biol Chem 277:11276–11283

    Article  CAS  PubMed  Google Scholar 

  40. Arnould T, Sellin L, Benzing T, Tsiokas L, Cohen HT, Kim E, Walz G (1999) Cellular activation triggered by the autosomal dominant polycystic kidney disease gene product PKD2. Mol Cell Biol 19:3423–3434

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Chapin HC, Caplan MJ (2010) The cell biology of polycystic kidney disease. J Cell Biol 191:701–710

    Article  CAS  PubMed  Google Scholar 

  42. Yoder BK, Hou X, Guay-Woodford LM (2002) The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol 13:2508–2516

    Article  CAS  PubMed  Google Scholar 

  43. Pazour GJ, Witman GB (2003) The vertebrate primary cilium is a sensory organelle. Curr Opin Cell Biol 15:105–110

    Article  CAS  PubMed  Google Scholar 

  44. Hogan MC, Manganelli L, Woollard JR, Masyuk AI, Masyuk TV, Tammachote R, Huang BQ, Leontovich AA, Beito TG, Madden BJ, Charlesworth MC, Torres VE, LaRusso NF, Harris PC, Ward CJ (2009) Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol 20:278–288

    Article  CAS  PubMed  Google Scholar 

  45. Tobin JL, Beales PL (2009) The nonmotile ciliopathies. Genet Med 11:386–402

    Article  CAS  PubMed  Google Scholar 

  46. Badano JL, Mitsuma N, Beales PL, Katsanis N (2006) The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 7:125–148

    Article  CAS  PubMed  Google Scholar 

  47. Woodward OM, Li Y, Yu S, Greenwell P, Wodarczyk C, Boletta A, Guggino WB, Qian F (2010) Identification of a polycystin-1 cleavage product, P100, that regulates store operated Ca entry through interactions with STIM1. PLoS One 5:e12305

    Article  PubMed Central  PubMed  Google Scholar 

  48. 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

    Article  CAS  PubMed  Google Scholar 

  49. Chapin HC, Rajendran V, Caplan MJ (2010) Polycystin-1 surface localization is stimulated by polycystin-2 and cleavage at the G Protein-coupled receptor proteolytic site. Mol Biol Cell 21:4338–4348

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Wei W, Hackmann K, Xu H, Germino G, Qian F (2007) Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J Biol Chem 282:21729–21737

    Article  CAS  PubMed  Google Scholar 

  51. Yu S, Hackmann K, Gao J, He X, Piontek K, Garcia-Gonzalez MA, Menezes LF, Xu H, Germino GG, Zuo J, Qian F (2007) Essential role of cleavage of polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proc Natl Acad Sci USA 104:18688–18693

    Article  CAS  PubMed  Google Scholar 

  52. Xu C, Rossetti S, Jiang L, Harris PC, Brown-Glaberman U, Wandinger-Ness A, Bacallao R, Alper SL (2007) Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling. Am J Physiol Renal Physiol 292:F930–F945

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ (2004) Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 114:1433–1443

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Bertuccio CA, Chapin HC, Cai Y, Mistry K, Chauvet V, Somlo S, Caplan MJ (2009) Polycystin-1 C-terminal cleavage is modulated by polycystin-2 expression. J Biol Chem 284:21011–21026

    Article  CAS  PubMed  Google Scholar 

  55. Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T (2006) Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 10:57–69

    Article  CAS  PubMed  Google Scholar 

  56. Rechsteiner M, Rogers SW (1996) PEST sequences and regulation by proteolysis. Trends Biochem Sci 21:267–271

    Article  CAS  PubMed  Google Scholar 

  57. Merrick D, Chapin H, Baggs JE, Yu Z, Somlo S, Sun Z, Hogenesch JB, Caplan MJ (2012) The gamma-secretase cleavage product of polycystin-1 regulates TCF and CHOP-mediated transcriptional activation through a p300-dependent mechanism. Dev Cell 22:197–210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Goilav B (2011) Apoptosis in polycystic kidney disease. Biochim Biophys Acta 1812:1272–1280

    Article  CAS  PubMed  Google Scholar 

  59. Lal B, Kapoor AK, Agrawal PK, Asthana OP, Srimal RC (2000) Role of curcumin in idiopathic inflammatory orbital pseudotumours. Phytother Res 14:443–447

    Article  CAS  PubMed  Google Scholar 

  60. Daugherty RL, Gottardi CJ (2007) Phospho-regulation of Beta-catenin adhesion and signaling functions. Physiology (Bethesda) 22:303–309

    Article  CAS  Google Scholar 

  61. Li J, Sutter C, Parker D, Blauwkamp T, Fang M, Cadigan K (2007) CBP/p300 are bimodal regulators of Wnt signaling. EMBO J 26:2284–2294

    Article  CAS  PubMed  Google Scholar 

  62. Wang X, Lawson B, Brewer J, Zinszner H, Sanjay A, Mi L, Boorstein R, Kreibich G, Hendershot L, Ron D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol 16:4273–4280

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Maytin E, Ubeda M, Lin J, Habener J (2001) Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp Cell Res 267:193–204

    Article  CAS  PubMed  Google Scholar 

  64. Kopito R (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10:524–530

    Article  CAS  PubMed  Google Scholar 

  65. Harding H, Calfon M, Urano F, Novoa I, Ron D (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–599

    Article  CAS  PubMed  Google Scholar 

  66. Wiertz E, Jones T, Sun L, Bogyo M, Geuze H, Ploegh H (1996) The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84:769–779

    Article  CAS  PubMed  Google Scholar 

  67. Nakatsukasa K, Brodsky J (2008) The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic 9:861–870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Ferri K, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3:E255–E263

    Article  CAS  PubMed  Google Scholar 

  69. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner B, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98–103

    Article  CAS  PubMed  Google Scholar 

  70. Ubeda M, Wang X, Zinszner H, Wu I, Habener J, Ron D (1996) Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element. Mol Cell Biol 16:1479–1489

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Ron D, Habener J (1992) CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev 6:439–453

    Article  CAS  PubMed  Google Scholar 

  72. Matsumoto M, Minami M, Takeda K, Sakao Y, Akira S (1996) Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Lett 395:143–147

    Article  CAS  PubMed  Google Scholar 

  73. Oyadomari S, Koizumi A, Takeda K, Gotoh T, Akira S, Araki E, Mori M (2002) Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest 109:525–532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Ohoka N, Hattori T, Kitagawa M, Onozaki K, Hayashi H (2007) Critical and functional regulation of CHOP (C/EBP homologous protein) through the N-terminal portion. J Biol Chem 282:35687–35694

    Article  CAS  PubMed  Google Scholar 

  75. Mangos S, Lam PY, Zhao A, Liu Y, Mudumana S, Vasilyev A, Liu A, Drummond IA (2010) The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Dis Model Mech 3:354–365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Arslanova D, Yang T, Xu X, Wong ST, Augelli-Szafran CE, Xia W (2010) Phenotypic analysis of images of zebrafish treated with Alzheimer’s gamma-secretase inhibitors. BMC Biotechnol 10:24

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all of the members of the Caplan laboratory past and present for helpful discussions and valuable input. Work from the authors’ laboratory that was discussed in this review was supported by Department of Defense Peer Reviewed Medical Research Program grant number W81XWH-10-1-0504 and by NIH grant P30 DK090744.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, P.O. Box 208026, New Haven, CT, 06520-8026, USA

    David Merrick, Claudia A. Bertuccio, Hannah C. Chapin, Mark Lal, Veronique Chauvet & Michael J. Caplan

Authors
  1. David Merrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudia A. Bertuccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hannah C. Chapin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Lal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Veronique Chauvet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael J. Caplan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Caplan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Merrick, D., Bertuccio, C.A., Chapin, H.C. et al. Polycystin-1 cleavage and the regulation of transcriptional pathways. Pediatr Nephrol 29, 505–511 (2014). https://doi.org/10.1007/s00467-013-2548-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-013-2548-y

Keywords

Search

Navigation