Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2009 Dec 25;28452:36431-36441. doi: 10.1074/jbc.M109.068916.
Show Gene links
Show Anatomy links
Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling with implications for polycystic kidney disease.
Li Y, Santoso NG, Yu S, Woodward OM, Qian F, Guggino WB.
???displayArticle.abstract???
The PKD1 or PKD2 genes encode polycystins (PC) 1 and 2, which are associated with polycystic kidney disease. Previously we demonstrated that PC2 interacts with the inositol 1,4,5-trisphosphate receptor (IP(3)R) to modulate Ca(2+) signaling. Here, we investigate whether PC1 also regulates IP(3)R. We generated a fragment encoding the last six transmembrane (TM) domains of PC1 and the C-terminal tail (QIF38), a section with the highest homology to PC2. Using a Xenopus oocyte Ca(2+) imaging system, we observed that expression of QIF38 significantly reduced the initial amplitude of IP(3)-induced Ca(2+) transients, whereas a mutation lacking the C-terminal tail did not. Thus, the C terminus is essential to QIF38 function. Co-immunoprecipitation assays demonstrated that through its C terminus, QIF38 associates with the IP(3)-binding domain of IP(3)R. A shorter PC1 fragment spanning only the last TM and the C-terminal tail also reduced IP(3)-induced Ca(2+) release, whereas another C-terminal fragment lacking any TM domain did not. Thus, only endoplasmic reticulum-localized PC1 can modulate IP(3)R. Finally, we show that in the polarized Madin-Darby canine kidney cells, heterologous expression of full-length PC1 resulted in a smaller IP(3)-induced Ca(2+) response. Overexpression of the IP(3)-binding domain of IP(3)R reversed the inhibitory effect of PC1, suggesting interaction of full-length PC1 (or its cleavage forms) with endogenous IP(3)R in Madin-Darby canine kidney cells. These results indicate that the behavior of full-length PC1 in mammalian cells is congruent with that of PC1 C-terminal fragments in the oocyte system. 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.
Aguiari,
Expression of polycystin-1 C-terminal fragment enhances the ATP-induced Ca2+ release in human kidney cells.
2003, Pubmed
Aguiari,
Expression of polycystin-1 C-terminal fragment enhances the ATP-induced Ca2+ release in human kidney cells.
2003,
Pubmed Aguiari,
Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.
2008,
Pubmed Ahrabi,
PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice.
2007,
Pubmed Anyatonwu,
Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2.
2007,
Pubmed Bezprozvanny,
The inositol 1,4,5-trisphosphate receptors.
2005,
Pubmed Bhunia,
PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2.
2002,
Pubmed Boletta,
Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells.
2000,
Pubmed Bosanac,
Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.
2002,
Pubmed Cai,
Identification and characterization of polycystin-2, the PKD2 gene product.
1999,
Pubmed Camandola,
Suppression of calcium release from inositol 1,4,5-trisphosphate-sensitive stores mediates the anti-apoptotic function of nuclear factor-kappaB.
2005,
Pubmed Chapman,
Autosomal dominant polycystic kidney disease: time for a change?
2007,
Pubmed Chernova,
Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl channel activity in Xenopus oocytes.
2005,
Pubmed
,
Xenbase Foggensteiner,
Cellular and subcellular distribution of polycystin-2, the protein product of the PKD2 gene.
2000,
Pubmed Gallagher,
Molecular basis of autosomal-dominant polycystic kidney disease.
2002,
Pubmed González-Perrett,
Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel.
2001,
Pubmed Grantham,
Lillian Jean Kaplan International Prize for advancement in the understanding of polycystic kidney disease. Understanding polycystic kidney disease: a systems biology approach.
2003,
Pubmed Grimm,
Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells.
2003,
Pubmed Hanaoka,
Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
,
Pubmed Hanaoka,
cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells.
2000,
Pubmed Hanaoka,
A role for CFTR in human autosomal dominant polycystic kidney disease.
1996,
Pubmed Hooper,
Expression of polycystin-1 enhances endoplasmic reticulum calcium uptake and decreases capacitative calcium entry in ATP-stimulated MDCK cells.
2005,
Pubmed Huan,
Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins.
1999,
Pubmed Ikeda,
Do polycystins function as cation channels?
2002,
Pubmed Jiang,
Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1.
2006,
Pubmed Kip,
[Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype.
2005,
Pubmed Koulen,
Polycystin-2 is an intracellular calcium release channel.
2002,
Pubmed Lantinga-van Leeuwen,
Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease.
2004,
Pubmed Li,
Ca2+-dependent redox modulation of SERCA 2b by ERp57.
2004,
Pubmed
,
Xenbase Li,
Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling.
2005,
Pubmed
,
Xenbase Lin,
Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins.
2005,
Pubmed Manzati,
The cytoplasmic C-terminus of polycystin-1 increases cell proliferation in kidney epithelial cells through serum-activated and Ca(2+)-dependent pathway(s).
2005,
Pubmed Nadasdy,
Proliferative activity of cyst epithelium in human renal cystic diseases.
1995,
Pubmed Nauli,
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.
2003,
Pubmed Newby,
Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex.
2002,
Pubmed O Bukanov,
Functional polycystin-1 expression is developmentally regulated during epithelial morphogenesis in vitro: downregulation and loss of membrane localization during cystogenesis.
2002,
Pubmed Pritchard,
A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype.
2000,
Pubmed Puri,
Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway.
2004,
Pubmed Qian,
Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells.
2003,
Pubmed Qian,
PKD1 interacts with PKD2 through a probable coiled-coil domain.
1997,
Pubmed Qian,
The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I.
1996,
Pubmed Qian,
Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations.
2002,
Pubmed Sandford,
The polycystins: a novel class of membrane-associated proteins involved in renal cystic disease.
1999,
Pubmed Sandford,
Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.
1997,
Pubmed Stokely,
Polycystin-1 can interact with homer 1/Vesl-1 in postnatal hippocampal neurons.
2006,
Pubmed Sutters,
Autosomal dominant polycystic kidney disease: molecular genetics and pathophysiology.
2003,
Pubmed Thivierge,
Overexpression of PKD1 causes polycystic kidney disease.
2006,
Pubmed Torres,
Autosomal dominant polycystic kidney disease.
2007,
Pubmed Tsiokas,
Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
1997,
Pubmed Vandorpe,
The cytoplasmic C-terminal fragment of polycystin-1 regulates a Ca2+-permeable cation channel.
2001,
Pubmed
,
Xenbase Watnick,
Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease.
1998,
Pubmed Weston,
Structure-function relationships of the extracellular domain of the autosomal dominant polycystic kidney disease-associated protein, polycystin-1.
2003,
Pubmed Wildman,
The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry.
2003,
Pubmed Wilson,
The PKD1 gene product, "polycystin-1," is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1-integrin in focal clusters in adherent renal epithelia.
1999,
Pubmed Wilson,
Polycystic kidney disease.
2004,
Pubmed Woo,
Apoptosis and loss of renal tissue in polycystic kidney diseases.
1995,
Pubmed Wu,
Somatic inactivation of Pkd2 results in polycystic kidney disease.
1998,
Pubmed Yamaguchi,
Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells.
2006,
Pubmed Ye,
The secretion of fluid by renal cysts from patients with autosomal dominant polycystic kidney disease.
1993,
Pubmed Yu,
Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure.
2007,
Pubmed Yuan,
Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors.
2003,
Pubmed Zatti,
The C-terminal tail of the polycystin-1 protein interacts with the Na,K-ATPase alpha-subunit.
2005,
Pubmed
