Myosin heavy-chain mutations that disrupt Caenorhabditis elegans thick filament assembly.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bejsovec, A; Anderson, P

Published Date

  • October 1, 1988

Published In

Volume / Issue

  • 2 / 10

Start / End Page

  • 1307 - 1317

PubMed ID

  • 3203908

Pubmed Central ID

  • 3203908

Electronic International Standard Serial Number (EISSN)

  • 1549-5477

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.2.10.1307

Language

  • eng