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J Biol Chem
2009 Dec 25;28452:36431-36441. doi: 10.1074/jbc.M109.068916.
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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
.
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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,
Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.
2008, Pubmed
Aguiari,
Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.
2008,
Pubmed
Aguiari,
Expression of polycystin-1 C-terminal fragment enhances the ATP-induced Ca2+ release in human kidney cells.
2003,
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,
cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells.
2000,
Pubmed
Hanaoka,
Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
,
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,
Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling.
2005,
Pubmed
,
Xenbase
Li,
Ca2+-dependent redox modulation of SERCA 2b by ERp57.
2004,
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,
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
Qian,
Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells.
2003,
Pubmed
Qian,
The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I.
1996,
Pubmed
Qian,
PKD1 interacts with PKD2 through a probable coiled-coil domain.
1997,
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,
Polycystic kidney disease.
2004,
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
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
