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Polycystin-2 (PC-2) is a non-selective cation channel that, when mutated, results in autosomal dominant polycystic kidney disease. In an effort to understand the regulation of this channel, we investigated the role of protein phosphorylation in PC-2 function. We demonstrated the direct incorporation of phosphate into PC-2 in cells and tissues and found that(More)
The most severe form of autosomal dominant polycystic kidney disease occurs in patients with mutations in the gene (PKD1) encoding polycystin-1 (PC1). PC1 is a complex polytopic membrane protein expressed in cilia that undergoes autoproteolytic cleavage at a G protein-coupled receptor proteolytic site (GPS). A quarter of PKD1 mutations are missense(More)
Mutations in polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease. A function for PC2 in the heart has not been described. Here, we show that PC2 coimmunoprecipitates with the cardiac ryanodine receptor (RyR2) from mouse heart. Biochemical assays showed that the N terminus of PC2 binds the RyR2, whereas the C terminus only binds to RyR2 in(More)
The homotetrameric structure of the ryanodine-sensitive intracellular calcium (Ca2+) release channel (ryanodine receptor (RyR)) suggests that the four RyR subunits either combine to form a single pore or that each RyR subunit is an independently conducting pathway. Previously we showed that methanethiosulfonate ethylammonium (MTSEA+) covalently modifies the(More)
Polycystin-2 (PC2), the gene product of one of two genes mutated in dominant polycystic kidney disease, is a member of the transient receptor potential cation channel family and can function as intracellular calcium (Ca(2+)) release channel. We performed a yeast two-hybrid screen by using the NH(2) terminus of PC2 and identified syntaxin-5 (Stx5) as a(More)
Polycystic kidney disease (PKD) is caused by mutations in two genes, PKD1 and PKD2, which encode for the proteins, polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Although disease-associated mutations have been identified in these two proteins, the sequence of molecular events leading up to clinical symptoms is still unknown. PC1 resides in the(More)
Polycystin-2 (PC2), a member of the transient receptor potential family of ion channels (TRPP2), forms a calcium-permeable cation channel. Mutations in PC2 lead to polycystic kidney disease. From the primary sequence and by analogy with other channels in this family, PC2 is modeled to have six transmembrane domains. However, most of the structural features(More)
Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores(More)
We have used limited trypsin digestion and reactivity with PEG-maleimides (MPEG) to study Ca(2+)-induced conformational changes of IP(3)Rs in their native membrane environment. We found that Ca(2+) decreased the formation of the 95-kDa C-terminal tryptic fragment when detected by an Ab directed at a C-terminal epitope (CT-1) but not with an Ab recognizing a(More)
To identify surface-accessible residues and monitor conformational changes of the type I inositol 1,4,5-trisphosphate receptor protein in membranes, we have introduced 10 cysteine substitutions into the N-terminal ligand-binding domain. The reactivity of these mutants with progressively larger maleimide-polyethylene glycol derivatives (MPEG) was measured(More)