Myosin heavy-chain mutations that disrupt Caenorhabditis elegans thick filament assembly.
We have investigated Caenorhabditis elegans mutants in which altered unc-54 myosin heavy-chain protein interferes with assembly of thick myofilaments. These mutants have a dominant, muscle-defective phenotype, because altered myosin heavy-chain B (MHC B), the product of the unc-54 gene, disrupts assembly of wild-type MHC B. The mutant MHC B also interferes with assembly of wild-type myosin heavy-chain A (MHC A), the product of another MHC gene expressed in body-wall muscle cells. Because of disrupted MHC A assembly, dominant unc-54 mutants also exhibit a recessive-lethal phenotype. Dominant unc-54 mutations are missense alleles, and the defects in thick filament assembly result from mutant protein that is of normal molecular weight. Accumulation of mutant MHC B in amounts as little as 2% of wild-type levels is sufficient to disrupt assembly of both wild-type MHC A and MHC B. Dominant unc-54 mutations occur at remarkably high frequency following ethylmethane sulfonate (EMS) mutagenesis; their frequency is approximately equal to that of recessive, loss-of-function mutations. This unusually high gain-of-function frequency implies that many different amino acid substitutions in the myosin heavy-chain B protein can disrupt thick filament assembly.
Bejsovec
A
A
Department of Genetics, University of Wisconsin, Madison 53706.
Anderson
P
P
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002107:Caenorhabditis / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005799:Genes, Dominant; D005804:Genes, Lethal; D009132:Muscles / Q000648:ultrastructure; D009154:Mutation; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics*; D013489:Suppression, Genetic
D009218:Myosins