Marston Steven, Mirza Mahmooda, Abdulrazzak Hassan, Sewry Caroline
National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK.
Neuromuscul Disord. 2004 Feb;14(2):167-74. doi: 10.1016/j.nmd.2003.11.003.
The mutation Met132Val in the ACTA1 gene was identified in a patient with mild nemaline myopathy (NM). We examined actin mRNA and protein from biopsy samples. Sixty-one percent of the mRNA from the biopsy was not cleaved with BstX1, indicating the presence of mutant messenger in vivo. Monomeric actin was extracted from 2.5 mg of mutant muscle and wild type muscle. A proportion of the NM actin did not polymerise in 50 mM KCl, 2.5 mM MgCl2 but all the wild-type actin did. NM actin was fully polymerised by 50 mM KCl, 2.5 mM MgCl2, 150 nM rhodamine-phalloidin. Thin filaments reconstituted with this co-polymer were different from wild-type. The NM actin produces faster sliding of thin filaments at pCa5 and higher relative isometric force. We conclude that the mutant mRNA and protein is expressed and that the mutation reduces polymerisability and alters thin filament function.
在一名患有轻度杆状体肌病（NM）的患者中，发现了ACTA1基因中的Met132Val突变。我们检测了活检样本中的肌动蛋白mRNA和蛋白质。活检样本中61%的mRNA未被BstX1切割，表明体内存在突变信使。从2.5mg突变型肌肉和野生型肌肉中提取单体肌动蛋白。一部分NM肌动蛋白在50mM KCl、2.5mM MgCl2中不会聚合，但所有野生型肌动蛋白都会聚合。NM肌动蛋白在50mM KCl、2.5mM MgCl2、150nM罗丹明 - 鬼笔环肽作用下完全聚合。用这种共聚物重构的细肌丝与野生型不同。在pCa5时，NM肌动蛋白使细肌丝滑动更快，且相对等长力更高。我们得出结论，突变的mRNA和蛋白质得以表达，且该突变降低了聚合能力并改变了细肌丝功能。
