Dystrophin is not essential for the integrity of the cytoskeleton
Dystrophin is not essential for the integrity of the cytoskeleton
复制标题
肌营养不良蛋白对于细胞骨架的完整性不是必需的
作者：
R. Massa;L. Castellani;G. Silvestri;G. Sancesario;G. Bernardi
肌营养不良蛋白定位于正常肌肉纤维的肌膜细胞质表面。该蛋白的功能尚不清楚，但根据其结构和细胞内分布，很可能是dystrophin与其他细胞骨架蛋白相互作用，在肌原纤维、肌膜和细胞外基质之间形成复杂的联系。为了评估dystrophin缺乏本身导致细胞骨架紊乱的可能性，我们研究了营养不良的mdx小鼠在开始坏死之前的一个阶段的肌纤维中这种结构的三个组成部分。用间接免疫荧光技术在冰冻切片上对肌膜结构中的纽蛋白、结蛋白和星云蛋白进行了染色。同样的单抗被用于从相同肌肉中提取的蛋白质的Western blotts中。比较18天龄的MDX小鼠和对照组小鼠的肌肉，发现这三种蛋白质的分布和相对丰度没有差异。我们的结果表明，缺乏dystrophin本身并不会导致连接肌膜和收缩装置的结构发生变化。无肌营养不良蛋白肌肉纤维的结构损伤最初可能局限于质膜的有限部分。这些局灶性病变破坏细胞内钙稳态，可导致肌肉纤维坏死。
Dystrophin is localized, in normal muscle fibers, on the cytoplasmic surface of the sarcolemma. The function of this protein is not known but, according to its structure and intracellular distribution, it seems likely that dystrophin interacts with other cytoskeletal proteins to form a complex linkage between myofibrils, sarcolemma and extracellular matrix. To evaluate the possibility that dystrophin deficiency induces, per se, a disarray in the cytoskeleton, we studied three components of this structure in muscle fibers of the dystrophic mdx mouse in a phase preceding the onset of necrosis. Vinculin, abundant in sarcolemmal structures called costameres, desmin, the principal component of intermediate filaments and nebulin, constituent of the socalled “third filament” within the sarcomere, were stained with the indirect immunofluorescence technique in cryostat sections. The same monoclonal antibodies were used in Western blots of proteins extracted from the same muscles. No difference was observed in the distribution or in the relative abundance of the three proteins, comparing muscles from 18 days-old mdx and control mice. Our results indicate that the lack of dystrophin does not induce, per se, alterations in the structures linking the sarcolemma to the contractile apparatus. It is likely that the structural damage in dystrophin-less muscle fibers is initially confined to limited portions of the plasma membrane. These focal lesions, impairing intracellular calcium homeostasis, can lead to muscle fiber necrosis.
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肌营养不良蛋白缺乏与坏死前和完全再生的骨骼肌中的肌腱连接缺陷有关。
DOI：
--
发表时间：
1993
期刊：
The American journal of pathology
影响因子：
--
作者：
Law,DJ;Tidball,JG
通讯作者：
Tidball,JG
细胞分级分离研究表明肌营养不良蛋白是骨骼肌表面膜的蛋白质。
DOI：
10.1042/bj2580837
发表时间：
1989
期刊：
The Biochemical journal
影响因子：
--
作者：
Salviati,G;Betto,R;Ceoldo,S;Biasia,E;Bonilla,E;Miranda,AF;Dimauro,S
通讯作者：
Dimauro,S
尽管抗肌营养不良蛋白缺乏的肌肉中净钙依赖性蛋白水解作用受到抑制，但钙蛋白酶浓度升高。
影响因子：
3.7
作者：
Spencer,MJ;Tidball,JG
通讯作者：
Tidball,JG
DOI：
10.1073/pnas.90.8.3710
发表时间：
1993-04-15
影响因子：
11.1
作者：
PETROF, BJ;SHRAGER, JB;SWEENEY, HL
通讯作者：
SWEENEY, HL