title: Requirement of the calcineurin subunit gene canB2 for indirect flight muscle formation in Drosophila.
abstract: Calcineurin is a calcium-activated protein phosphatase involved in multiple aspects of cardiac and skeletal muscle development and disease. Genes encoding calcineurin subunit proteins are highly conserved among animal species. Toward the goal of identifying new calcineurin-interacting loci that function in myogenic processes, we expressed an activated form of mouse calcineurin A in Drosophila and screened for suppressors of the phosphatase-induced lethality. Here, we demonstrate that a mutation in the canB2 gene, which encodes a regulatory subunit of Drosophila calcineurin, can suppress a pupal developmental arrest phenotype to adult viability. As canB2 is an essential gene and rare homozygous escapers are flightless, we further analyzed canB2 expression and function in pupae and adults. The gene is expressed in the forming indirect flight muscles and central nervous system during pupal development. A canA gene is comparably expressed in these tissues. Consistent with the observed muscle expression, canB2 mutants exhibit severe defects in the organization of their indirect flight muscles, a phenotype that is likely caused by muscle hypercontractility. Together, these findings demonstrate a vital role for the phosphatase in this specific facet of Drosophila myogenesis and show conserved fly and vertebrate calcineurin genes contribute prominently to fundamental processes of muscle formation and function.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gajewski
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Chen
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schulz
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D049452:Green Fluorescent Proteins; D006720:Homozygote; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019703:Calcineurin