trpp cation channels


Summary: A subgroup of TRP cation channels that are widely expressed in various cell types. Defects are associated with POLYCYSTIC KIDNEY DISEASES.

Top Publications

  1. Burtey S, Riera M, Ribe E, Pennenkamp P, Rance R, Luciani J, et al. Centrosome overduplication and mitotic instability in PKD2 transgenic lines. Cell Biol Int. 2008;32:1193-8 pubmed publisher
    ..PC-2 overexpression is associated with mitotic instability and centrosome overduplication. PC-2 therefore seems to play a role in centrosome duplication, and this hypothesis is being evaluated in other models. ..
  2. Battini L, Macip S, Fedorova E, Dikman S, Somlo S, Montagna C, et al. Loss of polycystin-1 causes centrosome amplification and genomic instability. Hum Mol Genet. 2008;17:2819-33 pubmed publisher
    ..These findings establish a novel function of PC1 in ADPKD pathogenesis and a genetic mechanism that may underlie the intrafamilial variability of ADPKD progression. ..
  3. Hoefele J, Mayer K, Scholz M, Klein H. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011;26:2181-8 pubmed publisher
    ..The increased number of known mutations will facilitate future studies into genotype-phenotype correlations. ..
  4. Fujimoto C, Ishimaru Y, Katano Y, Misaka T, Yamasoba T, Asakura T, et al. The single pore residue Asp523 in PKD2L1 determines Ca2+ permeation of the PKD1L3/PKD2L1 complex. Biochem Biophys Res Commun. 2011;404:946-51 pubmed publisher
    ..These results demonstrate that Asp(523) in PKD2L1 is a key determinant of Ca(2+) permeation into the PKD1L3/PKD2L1 complex and that PKD2L1 contributes to forming the pore of the PKD1L3/PKD2L1 channel. ..
  5. Pei Y, Obaji J, Dupuis A, Paterson A, Magistroni R, Dicks E, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol. 2009;20:205-12 pubmed publisher
    ..These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed. ..
  6. Ward H, Brown Glaberman U, Wang J, Morita Y, Alper S, Bedrick E, et al. A conserved signal and GTPase complex are required for the ciliary transport of polycystin-1. Mol Biol Cell. 2011;22:3289-305 pubmed publisher
    ..In this paper, we provide evidence for a conserved GTPase-dependent ciliary-trafficking mechanism that is shared between epithelia and neurons, and is essential in ciliary-trafficking and cell homeostasis. ..
  7. Bertuccio C, Chapin H, Cai Y, Mistry K, Chauvet V, Somlo S, et al. Polycystin-1 C-terminal cleavage is modulated by polycystin-2 expression. J Biol Chem. 2009;284:21011-26 pubmed publisher
    ..This effect is independent of Ca2+ but is regulated by sequences contained within the PC-2 C-terminal tail, suggesting a mechanism through which PC-1 and PC-2 may modulate a novel signaling pathway. ..
  8. Huang E, Samaniego Picota M, McCune T, Melancon J, Montgomery R, Ugarte R, et al. DNA testing for live kidney donors at risk for autosomal dominant polycystic kidney disease. Transplantation. 2009;87:133-7 pubmed publisher
    ..We show that DNA diagnostics can be used to enhance safe donation for certain living donor candidates at risk for ADPKD...
  9. Hoffmeister H, Babinger K, Gürster S, Cedzich A, Meese C, Schadendorf K, et al. Polycystin-2 takes different routes to the somatic and ciliary plasma membrane. J Cell Biol. 2011;192:631-45 pubmed publisher

More Information


  1. Li X. Phosphorylation, protein kinases and ADPKD. Biochim Biophys Acta. 2011;1812:1219-24 pubmed publisher
    ..The two proteins form a functional complex and prevent cyst formation, but the precise mechanism(s) involved remains unknown. This article is part of a Special Issue entitled: Polycystic Kidney Disease. ..
  2. Casuscelli J, Schmidt S, Degray B, Petri E, Celi A, Folta Stogniew E, et al. Analysis of the cytoplasmic interaction between polycystin-1 and polycystin-2. Am J Physiol Renal Physiol. 2009;297:F1310-5 pubmed publisher
    ..These results allow a more detailed understanding of the mechanism of pathogenic mutations in the cytoplasmic regions of PC1 and PC2...
  3. Huang K, Diener D, Mitchell A, Pazour G, Witman G, Rosenbaum J. Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella. J Cell Biol. 2007;179:501-14 pubmed
    ..These results suggest that the CrPKD2 cation channel is involved in coupling flagellar adhesion at the beginning of mating to the increase in flagellar calcium required for subsequent steps in mating. ..
  4. Du C, Zhang C, Hassan S, Biswas M, Balaji K. Protein kinase D1 suppresses epithelial-to-mesenchymal transition through phosphorylation of snail. Cancer Res. 2010;70:7810-9 pubmed publisher
    ..Together, our results suggest that PKD1 functions as a tumor and metastasis suppressor, at least partly by regulating Snail-mediated EMT, and that loss of PKD1 may contribute to acquisition of an aggressive malignant phenotype. ..
  5. Tan Y, Michaeel A, Blumenfeld J, Donahue S, Parker T, Levine D, et al. A novel long-range PCR sequencing method for genetic analysis of the entire PKD1 gene. J Mol Diagn. 2012;14:305-13 pubmed publisher
  6. Weimbs T. Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. Am J Physiol Renal Physiol. 2007;293:F1423-32 pubmed
    ..The existence of many known cellular and molecular similarities between renal repair and ADPKD supports this model. ..
  7. Petri E, Celic A, Kennedy S, Ehrlich B, Boggon T, Hodsdon M. 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;107:9176-81 pubmed publisher
    ..Based on our results, we present a mechanism of regulation of the Ca(2+) dependence of PC2 channel activity by PC2-EF. ..
  8. Takakura A, Contrino L, Zhou X, Bonventre J, Sun Y, Humphreys B, et al. Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum Mol Genet. 2009;18:2523-31 pubmed publisher
    ..These data demonstrate, for the first time, a role for polycystin-1 in kidney injury and repair and indicate that renal injury constitutes a 'third hit' resulting in rapid cyst formation in adulthood. ..
  9. Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol. 2009;71:83-113 pubmed publisher
    ..Their roles in primary cilia, shear stress sensation, alteration of intracellular calcium, and planar cell polarity are examined. The third-hit hypothesis of polycystic kidney disease is discussed. ..
  10. Winyard P, Jenkins D. Putative roles of cilia in polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1256-62 pubmed publisher
    ..Understanding how cilia fit into the other aspects of polycystic kidney disease biology is the challenge for the next decade. This article is part of a Special Issue entitled: Polycystic Kidney Disease...
  11. Li Y, Santoso N, Yu S, Woodward O, Qian F, Guggino W. Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling with implications for polycystic kidney disease. J Biol Chem. 2009;284:36431-41 pubmed publisher
    ..These data demonstrate that PC1 inhibits Ca(2+) release, perhaps opposing the effect of PC2, which facilitates Ca(2+) release through the IP(3)R. ..
  12. Bergmann C, von Bothmer J, Ortiz Brüchle N, Venghaus A, Frank V, Fehrenbach H, et al. Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. J Am Soc Nephrol. 2011;22:2047-56 pubmed publisher
    ..Our findings are consistent with a common pathogenesis and dosage theory for PKD and may propose a general concept for the modification of disease expression in other so-called monogenic disorders. ..
  13. Celic A, Petri E, Benbow J, Hodsdon M, Ehrlich B, Boggon T. Calcium-induced conformational changes in C-terminal tail of polycystin-2 are necessary for channel gating. J Biol Chem. 2012;287:17232-40 pubmed publisher
    ..We speculate that PC2 and the Ca(2+)-dependent transient receptor potential channels in general are regulated by similar conformational changes in their cytoplasmic domains that are propagated to the channel pore. ..
  14. Du J, Ding M, Sours Brothers S, Graham S, Ma R. Mediation of angiotensin II-induced Ca2+ signaling by polycystin 2 in glomerular mesangial cells. Am J Physiol Renal Physiol. 2008;294:F909-18 pubmed publisher
    ..These data suggest that PC2 selectively assembles with TRPC1 and TRPC4 to form channel complexes mediating ANG II-induced Ca(2+) responses in MCs. ..
  15. Wodarczyk C, Rowe I, Chiaravalli M, Pema M, Qian F, Boletta A. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS ONE. 2009;4:e7137 pubmed publisher
    ..We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases. ..
  16. Patel A, Honore E. Polycystins and renovascular mechanosensory transduction. Nat Rev Nephrol. 2010;6:530-8 pubmed publisher
    ..Finally, we discuss the possible role of altered mechanosensory transduction in the etiology of polycystic kidney disease. ..
  17. Gallagher A, Germino G, Somlo S. Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17:118-30 pubmed publisher
  18. Goilav B. Apoptosis in polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1272-80 pubmed publisher
    ..The purpose of this review is to outline the role of apoptosis in progression of PKD as well as to describe the mechanisms involved. This article is part of a Special Issue entitled: Polycystic Kidney Disease. ..
  19. Li X, Magenheimer B, Xia S, Johnson T, Wallace D, Calvet J, et al. A tumor necrosis factor-alpha-mediated pathway promoting autosomal dominant polycystic kidney disease. Nat Med. 2008;14:863-8 pubmed publisher
    ..These data reveal a pathway connecting TNF-alpha signaling, polycystins and cystogenesis, the activation of which may reduce functional polycystin-2 below a critical threshold, precipitating the ADPKD cellular phenotype...
  20. Yang B, Sonawane N, Zhao D, Somlo S, Verkman A. Small-molecule CFTR inhibitors slow cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2008;19:1300-10 pubmed publisher
    ..These results implicate CFTR in renal cyst growth and suggest that CFTR inhibitors may hold therapeutic potential to reduce cyst growth in PKD. ..
  21. Ibraghimov Beskrovnaya O, Bukanov N. Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies. Cell Mol Life Sci. 2008;65:605-19 pubmed
    ..We discuss available models and challenges for therapeutic discovery as well as summarize the results from preclinical experimental treatments targeting key disease-specific pathways. ..
  22. Franz Wachtel M, Eisler S, Krug K, Wahl S, Carpy A, Nordheim A, et al. Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics. 2012;11:160-70 pubmed publisher
    ..This study presents the first global detection of PKD1-dependent phosphorylation events and provides a wealth of information for functional follow-up of PKD1 activity upon disruption of the Golgi network in human cells...
  23. Spirli C, Locatelli L, Fiorotto R, Morell C, Fabris L, Pozzan T, et al. 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. 2012;55:856-68 pubmed publisher
    ..PLD, because of PC2 deficiency, represents the first example of human disease linked to the inappropriate activation of store-operated cAMP production. ..
  24. Hurd T, Zhou W, Jenkins P, Liu C, Swaroop A, Khanna H, et al. The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates cilia-mediated vertebrate development. Hum Mol Genet. 2010;19:4330-44 pubmed publisher
    ..This work suggests that RP2 may be an important regulator of ciliary function through its association with polycystin 2 and provides evidence of a further link between retinal and renal cilia function. ..
  25. Cornec Le Gall E, Audrezet M, Chen J, Hourmant M, Morin M, Perrichot R, et al. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013;24:1006-13 pubmed publisher
    ..This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value. ..
  26. Pei Y. Diagnostic approach in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2006;1:1108-14 pubmed
  27. Harris P, Rossetti S. Determinants of renal disease variability in ADPKD. Adv Chronic Kidney Dis. 2010;17:131-9 pubmed publisher
    ..Although ADPKD is a simple genetic disease, fully understanding the phenotypic variability requires consideration of influences at the genic, allelic, and genetic background level, and so, ultimately, it is complex. ..
  28. Leuenroth S, Bencivenga N, Chahboune H, Hyder F, Crews C. Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of ADPKD. Nephrol Dial Transplant. 2010;25:2187-94 pubmed publisher
  29. Driscoll J, Bhalla S, Liapis H, Ibricevic A, Brody S. Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest. 2008;133:1181-8 pubmed publisher
    ..This association suggests that patients with primary cilia-associated diseases may be at risk for airway disease. ..
  30. Weber K, Lee E, Basavanna U, Lindley S, Ziegelstein R, Germino G, et al. Heterologous expression of polycystin-1 inhibits endoplasmic reticulum calcium leak in stably transfected MDCK cells. Am J Physiol Renal Physiol. 2008;294:F1279-86 pubmed publisher
    ..We conclude that disruption of ER luminal calcium homeostasis may contribute to the cyst phenotype in autosomal dominant polycystic kidney disease. ..
  31. Yu Y, Ulbrich M, Li M, Buraei Z, Chen X, Ong A, et al. Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc Natl Acad Sci U S A. 2009;106:11558-63 pubmed publisher
    ..These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations. ..
  32. Giamarchi A, Feng S, Rodat Despoix L, Xu Y, Bubenshchikova E, Newby L, et al. A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes. EMBO J. 2010;29:1176-91 pubmed publisher
    ..Mutations that affect PC2 C-terminal homo- and heteromerization are the likely molecular basis of cyst formation in ADPKD. ..
  33. Ahrabi A, Terryn S, Valenti G, Caron N, Serradeil Le Gal C, Raufaste D, et al. PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol. 2007;18:1740-53 pubmed
    ..These data give new insights in the potential roles of polycystin-1 in the AVP and Ca(2+) signaling and the trafficking of AQP2 in the CD. ..
  34. Piontek K, Menezes L, Garcia Gonzalez M, Huso D, Germino G. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007;13:1490-5 pubmed
    ..These results have important implications for clinical understanding of the disease and therapeutic approaches. ..
  35. Fedeles S, Tian X, Gallagher A, Mitobe M, Nishio S, Lee S, et al. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet. 2011;43:639-47 pubmed publisher
  36. Choi Y, Suzuki A, Hajarnis S, Ma Z, Chapin H, Caplan M, et al. 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 U S A. 2011;108:10679-84 pubmed publisher
  37. Aguiari G, Trimi V, Bogo M, Mangolini A, Szabadkai G, Pinton P, et al. Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. Cell Prolif. 2008;41:554-73 pubmed publisher
  38. O Leary C, Duffy D, Biros I, Corley S. Linkage confirms canine pkd1 orthologue as a candidate for bull terrier polycystic kidney disease. Anim Genet. 2009;40:543-6 pubmed publisher
    ..A highly significant multi-point LOD score that peaked over the canine pkd1 locus was observed (LOD = 6.59, best two-point LOD score LOD = 6.02), implicating this as the BTPKD locus. ..
  39. Patel V, Chowdhury R, Igarashi P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr Opin Nephrol Hypertens. 2009;18:99-106 pubmed publisher
    ..Mouse models of PKD, especially those with mutations in genes that are orthologous to human disease genes, have provided insights into the pathogenesis of cyst formation and advanced the preclinical testing of new drugs...
  40. Li X. Epigenetics and autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1213-8 pubmed publisher
    ..This article is part of a Special Issue entitled: Polycystic Kidney Disease. ..
  41. Xiao Z, Zhang S, Cao L, Qiu N, David V, Quarles L. Conditional disruption of Pkd1 in osteoblasts results in osteopenia due to direct impairment of bone formation. J Biol Chem. 2010;285:1177-87 pubmed publisher
    ..The conditional deletion of Pkd1 also resulted in increased adipogenesis in bone marrow and in osteoblast cultures. Thus, PKD1 directly functions in osteoblasts to regulate bone formation. ..
  42. Hartman T, Liu D, Zilfou J, Robb V, Morrison T, Watnick T, et al. The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway. Hum Mol Genet. 2009;18:151-63 pubmed publisher
    ..Our data link the TSC proteins with the primary cilium and reveal a novel phenotype of enhanced ciliary formation in a cyst-associated disease...
  43. Boucher C, Ward H, Case R, Thurston K, Li X, Needham A, et al. Receptor protein tyrosine phosphatases are novel components of a polycystin complex. Biochim Biophys Acta. 2011;1812:1225-38 pubmed publisher
    ..This article is part of a Special Issue entitled: Polycystic Kidney Disease. ..
  44. Prasad S, McDaid J, Tam F, Haylor J, Ong A. Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury. Am J Pathol. 2009;175:1493-503 pubmed publisher
    ..Polycystin-2 is therefore likely to play multiple roles in regulating tubular cell viability, repair, and remodeling in the mature kidney...
  45. Santoso N, Cebotaru L, Guggino W. Polycystin-1, 2, and STIM1 interact with IP(3)R to modulate ER Ca release through the PI3K/Akt pathway. Cell Physiol Biochem. 2011;27:715-26 pubmed publisher
    ..Overall, our studies provide a potential mechanism for the modulation of intracellular Ca(2+) signaling by the polycystins. ..
  46. Nauli S, Kawanabe Y, Kaminski J, Pearce W, Ingber D, Zhou J. Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation. 2008;117:1161-71 pubmed publisher
    ..We propose that a distinctive communication with the extracellular microenvironment depends on the proper localization and function of polycystin-1 in cilia. ..
  47. Yu C, Yang Y, Zou L, Hu Z, Li J, Liu Y, et al. Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease. BMC Med Genet. 2011;12:164 pubmed publisher
    ..Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease. ..
  48. Shibazaki S, Yu Z, Nishio S, Tian X, Thomson R, Mitobe M, et al. Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1. Hum Mol Genet. 2008;17:1505-16 pubmed publisher
    ..Cysts in ADPKD exhibit both increased proliferation and activation of MAPK/ERK, but cyst growth is not prevented by inhibition of ERK1/2 activation. ..
  49. Luyten A, Su X, Gondela S, Chen Y, Rompani S, Takakura A, et al. Aberrant regulation of planar cell polarity in polycystic kidney disease. J Am Soc Nephrol. 2010;21:1521-32 pubmed publisher
    ..Taken together, our data suggest that PC1 controls oriented cell division and that aberrant PCP signaling contributes to cystogenesis...
  50. Sharma N, Malarkey E, Berbari N, O Connor A, Vanden Heuvel G, Mrug M, et al. Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption. J Am Soc Nephrol. 2013;24:456-64 pubmed publisher
    ..In conclusion, these data suggest that proliferation is unlikely to be the sole mechanism underlying the rapid cystogenesis observed after injury in mice that lose cilia function in adulthood. ..
  51. Kim I, Ding T, Fu Y, Li C, Cui L, Li A, et al. Conditional mutation of Pkd2 causes cystogenesis and upregulates beta-catenin. J Am Soc Nephrol. 2009;20:2556-69 pubmed publisher
    ..Our results suggest that loss of PC2 disrupts normal behavior of renal epithelial cells through dysregulation of beta-catenin-dependent signaling, revealing a potential role for this signaling pathway in PC2-associated ADPKD. ..
  52. Lantinga van Leeuwen I, Leonhard W, van der Wal A, Breuning M, De Heer E, Peters D. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet. 2007;16:3188-96 pubmed
    ..Furthermore, we show that one germ-line mutation of Pkd1 is already associated with increased proliferation. ..
  53. Vujic M, Heyer C, Ars E, Hopp K, Markoff A, Orndal C, et al. Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD. J Am Soc Nephrol. 2010;21:1097-102 pubmed publisher
    ..Furthermore, the phenotypic overlap between ARPKD and these patients resulting from incomplete penetrant PKD1 alleles support a common pathogenesis for these diseases. ..