Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence
Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence
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DOI：
10.1074/jbc.270.52.31158
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发表时间：
1995-12-29
影响因子：
4.8
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Sorimachi, H;Kinbara, K;Suzuki, K
p94是钙蛋白酶家族的肌肉特异性成员，其独特之处在于其经历快速和彻底的自溶，半衰期小于1小时，导致其从肌肉中消失。最近，p94被证明是负责肢带型肌营养不良症2A型。为了阐明p94介导的肌肉蛋白水解系统，并解决其异常快速自溶的奥秘，我们用双杂交系统寻找p94结合蛋白。虽然钙蛋白酶小亚基在调节普遍存在的钙蛋白酶中起着至关重要的作用，但它与p94无关。在骨骼肌文库的筛选之后，发现连接蛋白（或肌联蛋白），一种跨越肌肉肌节的M-至Z-线的巨大丝状蛋白，通过p94特异性区域IS 2与p94结合。连接蛋白不溶性部分洗涤肌原纤维含有全长完整的p94，这表明连接蛋白调节p94活性。
p94, a muscle-specific member of calpain family, is unique in that it undergoes rapid and exhaustive autolysis with a half-life of less than 1 h resulting in its disappearance from muscle. Recently, p94 was shown to be responsible for limb girdle muscular dystrophy type 2A. To elucidate the muscular proteolytic system mediated by p94 and to solve the mystery of its unusually rapid autolysis, we searched for p94-binding proteins by the two hybrid system. Although calpain small subunit plays a crucial role for regulation of ubiquitous calpains, it did not associate with p94. After a screening of skeletal muscle library, connectin (or titin), a gigantic filamentous protein spanning the M- to Z-lines of muscle sarcomere, was found to bind to p94 through a p94-specific region, IS2. The connectin-insoluble fraction of washed myofibrils contained full-length intact p94, suggesting that connectin regulates p94 activity.