© The Rockefeller University Press,
0021-9525/1999//989 $5.00
The Journal of Cell Biology, Volume 144, Number 5,
, 1999 989-1000
Specific Myosin Heavy Chain Mutations Suppress Troponin I Defects in Drosophila Muscles
William A. Kronert*,
Angel Acebes
,
Alberto Ferrús
, and
Sanford I. Bernstein*
* Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, California 92182-4614; and
Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid 28002, Spain
We show that specific mutations in the head of the thick filament molecule myosin heavy chain prevent a degenerative muscle syndrome resulting from the hdp2 mutation in the thin filament protein troponin I. One mutation deletes eight residues from the actin binding loop of myosin, while a second affects a residue at the base of this loop. Two other mutations affect amino acids near the site of nucleotide entry and exit in the motor domain. We document the degree of phenotypic rescue each suppressor permits and show that other point mutations in myosin, as well as null mutations, fail to suppress the hdp2 phenotype. We discuss mechanisms by which the hdp2 phenotypes are suppressed and conclude that the specific residues we identified in myosin are important in regulating thick and thin filament interactions. This in vivo approach to dissecting the contractile cycle defines novel molecular processes that may be difficult to uncover by biochemical and structural analysis. Our study illustrates how expression of genetic defects are dependent upon genetic background, and therefore could have implications for understanding gene interactions in human disease.
Key Words: Drosophila muscle myosin myofibril troponin I
Abbreviations used in this paper: Su(hdp2)D; DLM, dorsolongitudinal muscle; MHC, myosin heavy chain; Mhc, myosin heavy chain gene.
We appreciate the help of Dr. Ronald Milligan (The Scripps Research Institute) in preparation of Fig. 2. We thank Drs. Richard Cripps (University of New Mexico), Larry Tobacman (University of Iowa), and Douglas Swank (San Diego State University) for helpful comments on the manuscript.
This research was supported by grants from the Muscular Dystrophy Association and the National Institutes of Health (GM32443) to S.I. Bernstein, and from the Direccion General de Investigacíon Cientifica y Técnica (Spanish Ministry of Culture; PM96-0006) to A. Ferrús.

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