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• W2138714101 abstract "Autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) colocalize in the apical monocilia of renal epithelial cells. Mouse and human renal cells without PC1 protein show impaired ciliary mechanosensation, and this impairment has been proposed to promote cystogenesis. However, most cyst epithelia of human ADPKD kidneys appear to express full-length PC1 and PC2 in normal or increased abundance. We show that confluent primary ADPKD cyst cells with the novel PC1 mutation DeltaL2433 and with normal abundance of PC1 and PC2 polypeptides lack ciliary PC1 and often lack ciliary PC2, whereas PC1 and PC2 are both present in cilia of confluent normal human kidney (NK) epithelial cells in primary culture. Confluent NK cells respond to shear stress with transient increases in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), dependent on both extracellular Ca(2+) and release from intracellular stores. In contrast, ADPKD cyst cells lack flow-sensitive [Ca(2+)](i) signaling and exhibit reduced endoplasmic reticulum Ca(2+) stores and store-depletion-operated Ca(2+) entry but retain near-normal [Ca(2+)](i) responses to ANG II and to vasopressin. Expression of wild-type and mutant CD16.7-PKD1(115-226) fusion proteins reveals within the COOH-terminal 112 amino acids of PC1 a coiled-coil domain-independent ciliary localization signal. However, the coiled-coil domain is required for CD16.7-PKD1(115-226) expression to accelerate decay of the flow-induced Ca(2+) signal in NK cells. These data provide evidence for ciliary dysfunction and polycystin mislocalization in human ADPKD cells with normal levels of PC1." @default.
• W2138714101 created "2016-06-24" @default.
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• W2138714101 date "2007-03-01" @default.
• W2138714101 modified "2023-10-16" @default.
• W2138714101 title "Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the <i>PKD1</i> gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca²⁺ signaling" @default.
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• W2138714101 doi "https://doi.org/10.1152/ajprenal.00285.2006" @default.
• W2138714101 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3586432" @default.
• W2138714101 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17090781" @default.
• W2138714101 hasPublicationYear "2007" @default.
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