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10.1242/jcs.176065

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suck abstract from ncbi


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pmid26546361
      J+Cell+Sci 2015 ; 128 (24 ): 4550-9
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  • Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis #MMPMID26546361
  • Slaats GG ; Wheway G ; Foletto V ; Szymanska K ; van Balkom BW ; Logister I ; Den Ouden K ; Keijzer-Veen MG ; Lilien MR ; Knoers NV ; Johnson CA ; Giles RH
  • J Cell Sci 2015[Dec]; 128 (24 ): 4550-9 PMID26546361 show ga
  • To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p.R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function of KCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches.
  • |Animals [MESH]
  • |Cell Line [MESH]
  • |Cilia/genetics/metabolism [MESH]
  • |Humans [MESH]
  • |Kidney Tubules, Collecting/*metabolism/pathology [MESH]
  • |Mice [MESH]
  • |Potassium Channels/genetics/*metabolism [MESH]


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