MYOSIN HEAVY-CHAIN MUTATIONS THAT DISRUPT CAENORHABDITIS-ELEGANS THICK FILAMENT ASSEMBLY
MYOSIN HEAVY-CHAIN MUTATIONS THAT DISRUPT CAENORHABDITIS-ELEGANS THICK FILAMENT ASSEMBLY
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DOI：
10.1101/gad.2.10.1307
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发表时间：
1988-10-01
影响因子：
10.5
通讯作者：
ANDERSON, P
中科院分区：
文献类型：
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作者：
BEJSOVEC, A;ANDERSON, P
我们研究了秀丽隐杆线虫突变体，其中改变的unc-54肌球蛋白重链蛋白干扰了粗肌丝的组装。这些突变体具有显性的肌肉缺陷表型，因为改变的肌球蛋白重链B (MHC B)， unc-54基因的产物，破坏了野生型MHC B的组装。突变的MHC B也干扰了野生型肌球蛋白重链a （MHC a）的组装，MHC a是在体壁肌肉细胞中表达的另一种MHC基因的产物。由于MHC A组装被破坏，显性unc-54突变体也表现出隐性致死表型。unc-54显性突变为错义等位基因，粗丝装配缺陷是由分子量正常的突变蛋白引起的。突变型MHC B的积累量仅为野生型MHC A和MHC B的2%，足以破坏野生型MHC A和MHC B的组装。在乙基甲烷磺酸盐（EMS）突变后，显性unc-54突变发生的频率非常高；它们的频率与隐性、功能丧失突变的频率大致相等。这种不同寻常的高功能增益频率意味着肌球蛋白重链B蛋白中许多不同的氨基酸取代可以破坏粗丝的组装。
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 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.