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Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila.

Publication ,  Journal Article
Lee, TE; Yu, L; Wolf, MJ; Rockman, HA
Published in: Genetics
October 2014

Activated/uninhibited calcineurin is both necessary and sufficient to induce cardiac hypertrophy, a condition that often leads to dilated cardiomyopathy, heart failure, and sudden cardiac death. We expressed constitutively active calcineurin in the adult heart of Drosophila melanogaster and identified enlarged cardiac chamber dimensions and reduced cardiac contractility. In addition, expressing constitutively active calcineurin in the fly heart using the Gal4/UAS system induced an increase in heart wall thickness. We performed a targeted genetic screen for modifiers of calcineurin-induced cardiac enlargement based on previous calcineurin studies in the fly and identified galactokinase as a novel modifier of calcineurin-induced cardiomyopathy. Genomic deficiencies spanning the galactokinase locus, transposable elements that disrupt galactokinase, and cardiac-specific RNAi knockdown of galactokinase suppressed constitutively active calcineurin-induced cardiomyopathy. In addition, in flies expressing constitutively active calcineurin using the Gal4/UAS system, a transposable element in galactokinase suppressed the increase in heart wall thickness. Finally, genetic disruption of galactokinase suppressed calcineurin-induced wing vein abnormalities. Collectively, we generated a model for discovering novel modifiers of calcineurin-induced cardiac enlargement in the fly and identified galactokinase as a previously unknown regulator of calcineurin-induced cardiomyopathy in adult Drosophila.

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Published In

Genetics

DOI

EISSN

1943-2631

Publication Date

October 2014

Volume

198

Issue

2

Start / End Page

591 / 603

Location

United States

Related Subject Headings

  • Myocardium
  • Membrane Proteins
  • Male
  • Galactokinase
  • Female
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology
  • Cardiomyopathy, Dilated
  • Calcineurin
 

Citation

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Lee, T. E., Yu, L., Wolf, M. J., & Rockman, H. A. (2014). Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila. Genetics, 198(2), 591–603. https://doi.org/10.1534/genetics.114.166777
Lee, Teresa E., Lin Yu, Matthew J. Wolf, and Howard A. Rockman. “Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila.Genetics 198, no. 2 (October 2014): 591–603. https://doi.org/10.1534/genetics.114.166777.
Lee TE, Yu L, Wolf MJ, Rockman HA. Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila. Genetics. 2014 Oct;198(2):591–603.
Lee, Teresa E., et al. “Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila.Genetics, vol. 198, no. 2, Oct. 2014, pp. 591–603. Pubmed, doi:10.1534/genetics.114.166777.
Lee TE, Yu L, Wolf MJ, Rockman HA. Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila. Genetics. 2014 Oct;198(2):591–603.

Published In

Genetics

DOI

EISSN

1943-2631

Publication Date

October 2014

Volume

198

Issue

2

Start / End Page

591 / 603

Location

United States

Related Subject Headings

  • Myocardium
  • Membrane Proteins
  • Male
  • Galactokinase
  • Female
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology
  • Cardiomyopathy, Dilated
  • Calcineurin