Defects in the Drosophila myosin rod permit sarcomere assembly but cause flight muscle degeneration.
We have determined the molecular and ultrastructural defects associated with three homozygous-viable myosin heavy chain mutations of Drosophila melanogaster. These mutations cause a dominant flightless phenotype but allow relatively normal assembly of indirect flight muscle myofibrils. As adults age, the contents of the indirect flight muscle myofibers are pulled to one end of the thorax. This apparently results from myofibril "hyper-contraction", and leads to sarcomere rupture and random myofilament orientation. All three mutations cause single amino acid changes in the light meromyosin region of the myosin rod. Two change the same glutamic acid to a lysine residue and the third affects an amino acid five residues away, substituting histidine for arginine. Both affected residues are conserved in muscle myosins, cytoplasmic myosins and paramyosins. The mutations are associated with age-dependent, site-specific degradation of myosin heavy chain and failure to accumulate phosphorylated forms of flightin, an indirect flight muscle-specific protein previously localized to the thick filament. Given the repeating nature of the hydrophobic and charged amino acid residues of the myosin rod and the near-normal assembly of myofibrils in the indirect flight muscle of these mutants, it is remarkable that single amino acid changes in the rod cause such severe defects. It is also interesting that these severe defects are not apparent in other muscles. These phenomena likely arise from the highly organized nature and rigorous performance requirements of indirect flight muscle, and perhaps from the interaction of myosin with flightin, a protein specific to this muscle type.
Kronert
W A
WA
Department of Biology, San Diego State University, CA 92182-4614, USA.
O'Donnell
P T
PT
Fieck
A
A
Lawn
A
A
Vigoreaux
J O
JO
Sparrow
J C
JC
Bernstein
S I
SI
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004331:Drosophila melanogaster / Q000502:physiology*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure
D009218:Myosins