Beall C J, Fyrberg E
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
J Cell Biol. 1991 Sep;114(5):941-51. doi: 10.1083/jcb.114.5.941.
We have investigated the molecular bases of muscle abnormalities in four Drosophila melanogaster heldup mutants. We find that the heldup gene encodes troponin-I, one of the principal regulatory proteins associated with skeletal muscle thin filaments. heldup3, heldup4, and heldup5 mutants, all of which have grossly abnormal flight muscle myofibrils, lack mRNAs encoding one or more troponin-I isoforms. In contrast, heldup2, an especially interesting mutant wherein flight muscles are atrophic, synthesizes the complete mRNA complement. By sequencing mutant troponin-I cDNAs we demonstrate that the molecular basis for muscle degeneration in heldup2 is conversion of an invariant alanine residue to valine. We finally show that degeneration of heldup2 thin filament/Z-disc networks can be prevented by eliminating thick filaments from flight muscles using a null allele of the sarcomeric myosin heavy chain gene. This latter observation suggests that actomyosin interactions exacerbate the structural or functional defect resulting from the troponin-I mutation.
我们研究了四种果蝇heldup突变体中肌肉异常的分子基础。我们发现heldup基因编码肌钙蛋白I，它是与骨骼肌细肌丝相关的主要调节蛋白之一。heldup3、heldup4和heldup5突变体的飞行肌肌原纤维都严重异常，缺乏编码一种或多种肌钙蛋白I同工型的mRNA。相比之下，heldup2是一个特别有趣的突变体，其飞行肌萎缩，能合成完整的mRNA互补序列。通过对突变型肌钙蛋白I cDNA进行测序，我们证明heldup2中肌肉退化的分子基础是一个不变的丙氨酸残基转变为缬氨酸。我们最终表明，利用肌节肌球蛋白重链基因的无效等位基因从飞行肌中消除粗肌丝，可以防止heldup2细肌丝/Z盘网络的退化。后一项观察结果表明，肌动球蛋白相互作用加剧了肌钙蛋白I突变导致的结构或功能缺陷。
