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Citation
Akasaka, T., Klinedinst, S., Ocorr, K., Bustamante, E.L., Kim, S.K., Bodmer, R. (2006). The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman.  Proc. Natl. Acad. Sci. U.S.A. 103(32): 11999--12004.
FlyBase ID
FBrf0193639
Publication Type
Research paper
Abstract

The homeobox transcription factor Tinman plays an important role in the initiation of heart development. Later functions of Tinman, including the target genes involved in cardiac physiology, are less well studied. We focused on the dSUR gene, which encodes an ATP-binding cassette transmembrane protein that is expressed in the heart. Mammalian SUR genes are associated with K(ATP) (ATP-sensitive potassium) channels, which are involved in metabolic homeostasis. We provide experimental evidence that Tinman directly regulates dSUR expression in the developing heart. We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium. Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo. Physiological analysis of dSUR knock-down flies supports the idea that dSUR plays a protective role against hypoxic stress and pacing-induced heart failure. Because dSUR expression dramatically decreases with age, it is likely to be a factor involved in the cardiac aging phenotype of Drosophila. dSUR provides a model for addressing how embryonic regulators of myocardial cell commitment can contribute to the establishment and maintenance of cardiac performance.

PubMed ID
PubMed Central ID
PMC1567687 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (33)
    Genes (12)
    Sequence Features (2)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (1)
    Transgenic Constructs (32)