DYSFERLIN ASSOCIATES WITH THE DEVELOPING T-TUBULE SYSTEM IN RODENT AND HUMAN SKELETAL MUSCLE
DYSFERLIN ASSOCIATES WITH THE DEVELOPING T-TUBULE SYSTEM IN RODENT AND HUMAN SKELETAL MUSCLE
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DOI：
10.1002/mus.21166
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发表时间：
2010-02-01
期刊：
影响因子：
3.4
通讯作者：
Bushby, Kate
中科院分区：
文献类型：
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作者：
Klinge, Lars;Harris, John;Bushby, Kate
异常铁蛋白基因突变导致213型肢带肌营养不良症、三良肌病和远端前室肌病。异铁蛋白主要定位于成熟骨骼肌的肌膜，参与膜融合和修复。在不同形式的肌肉萎缩症中，在再生肌纤维中可以观察到异常蛋白的主要细胞质定位，但负责这种标记模式的亚细胞区室尚不清楚。我们之前已经在体外证明了异铁素与发育中的t小管系统的关联。为了研究异铁素在成人骨骼肌再生中的作用，我们在大鼠再生模型中以高分辨率研究了异铁素的定位，发现异铁素的亚细胞标记与发育中的t小管系统共定位。此外，超微结构分析显示，异常蛋白缺乏肌肉的原发性t小管异常与小窝蛋白-3缺乏肌肉相似。这些发现表明，异常铁蛋白是正确t小管形成所必需的，而异常铁蛋白缺乏的骨骼肌的特征是异常配置的t小管。肌肉神经学报，2010
Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 213, Miyoshi myopathy, and distal anterior compartment myopathy. Dysferlin mainly localizes to the sarcolemma in mature skeletal muscle where it is implicated in membrane fusion and repair. In different forms of muscular dystrophy, a predominantly cytoplasmic localization of dysferlin can be observed in regenerating myofibers, but the subcellular compartment responsible for this labeling pattern is not yet known. We have previously demonstrated an association of dysferlin with the developing T-tubule system in vitro. To investigate the role of dysferlin in adult skeletal muscle regeneration, we studied dysferlin localization at high resolution in a rat model of regeneration and found that the subcellular labeling of dysferlin colocalizes with the developing T-tubule system. Furthermore, ultrastructural analysis of dysferlin-deficient muscle revealed primary T-tubule anomalies similar to those seen in caveolin-3-deficient muscle. These findings indicate that dysferlin is necessary for correct T-tubule formation, and dysferlin-deficient skeletal muscle is characterized by abnormally configured T-tubules. Muscle Nerve : 166-173, 2010