title: A charge change in an evolutionarily-conserved region of the myosin globular head prevents myosin and thick filament accumulation in Drosophila.
abstract: We have determined the molecular lesion in Mhc9, a homozygous-viable mutant of the Drosophila muscle myosin heavy chain gene. This mutation is in an adult-specific alternative exon (exon 9a) which encodes a portion of the myosin head that is highly conserved among both cytoplasmic and muscle myosins of all organisms. The mutation results in a charge change in the evolutionarily invariant amino acid residue 482. The phenotype of the homozygous mutant is identical to that of an organism having a stop codon within alternative exon 9a, i.e. lack of thick filaments in the indirect flight muscles and a greatly reduced number of thick filaments in the small cells of the jump muscles. This phenotype correlates with the known expression pattern of exon 9a. Genetic, biochemical and ultrastructural analyses show that the failure to accumulate thick filaments in the mutant is not a result of aberrant interactions with thin filaments and that the mutant myosin heavy chain does not poison assembly of wild-type thick filaments. Our results, in conjunction with recent structural and mutant studies by others, indicate that residue 482 is important for generating ATPase activity and for myosin stability in muscle.
authors.affiliation: Biology Department, San Diego State University, CA 92182.
authors.forename: W A
authors.initials: WA
authors.lastname: Kronert
authors.forename: P T
authors.initials: PT
authors.lastname: O'Donnell
authors.forename: S I
authors.initials: SI
authors.lastname: Bernstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure; D009218:Myosins / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D009218:Myosins