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Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila

Title:

Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila

Gamberi, Chiara ORCID: https://orcid.org/0000-0002-7122-6491, Hipfner, David R., Trudel, Marie and Lubell, William D. (2017) Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila. PLoS Genetics .

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Official URL: https://doi.org/10.1371/journal.pgen.1006694

Abstract

Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called ªMalpighianº tubules) and reduced renal function. The BicC protein was shown to bind to Drosophila (d-) myc mRNA in tubules. Elevation of d-Myc protein levels was a cause of tubular degeneration in BicC mutants. Activation of the Target of Rapamycin (TOR) kinase pathway, another common feature of PKD, was found in BicC mutant flies. Rapamycin administration substantially reduced the cystic phenotype in flies. We present new mechanistic insight on BicC function and propose that Drosophila may serve as a genetically tractable model for dissecting the evolutionarily-conserved molecular mechanisms of renal cystogenesis.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Article
Refereed:Yes
Authors:Gamberi, Chiara and Hipfner, David R. and Trudel, Marie and Lubell, William D.
Journal or Publication:PLoS Genetics
Date:13 April 2017
Funders:
  • Natural Sciences and Engineering Research Council of Canada (NSERC)
  • The Polycystic Kidney Disease Foundation
  • Canadian Institute for Health Research (CIHR)
  • Concordia University Part time Faculty Association Professional Development Award
Digital Object Identifier (DOI):10.1371/journal.pgen.1006694
ID Code:985018
Deposited By: CHIARA GAMBERI
Deposited On:26 Feb 2019 19:36
Last Modified:26 Feb 2019 19:36
Related URLs:

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