Differential Membrane Localization and Intermolecular Associations of α-Dystrobrevin Isoforms in Skeletal Muscle
Differential Membrane Localization and Intermolecular Associations of α-Dystrobrevin Isoforms in Skeletal Muscle
复制标题
骨骼肌中 α-Dystrobrevin 亚型的差异膜定位和分子间关联
作者：
M. F. Peters;Hélène M. Sadoulet;R. Mark Grady;N. Kramarcy;L. Kunkel;J. Sanes;R. Sealock;S. Froehner
α-Dystrobrevin既是抗肌营养不良蛋白的同系物，也是抗肌营养不良蛋白复合体的组成部分。选择性剪接产生五种形式，其中两种在骨骼肌中占主导地位：全长α-dystrobrevin-1(84kD)和COOH端截短的α-dystrobrevin-2(65kD)。利用异构体特异性抗体，我们发现α-dystrobrevin-2定位于肌膜和神经肌肉突触，与dystrophin一样，它最集中在连接后皱折的深处。α-Dystrobrevin-2优先与肌肉提取物中的Dystrophin交配。相反，α-dystrobrevin-1更多地局限于突触，就像dystrophin同系物utroin一样，并优先与utroin交配。在酵母双杂交实验和体外翻译蛋白的免疫共沉淀中，α-dystrobrevin-2结合dystrophin，而α-dystrobrevin-1结合dystrophin和utroin。α-Dystrobrevin-2在Dystrophin缺陷型mdx小鼠的非突触肌膜中丢失，但即使在缺乏utroin和dystrophin的小鼠的突触周围肌膜上仍保留。相反，α-dystrobrevin-1仍然定位于mdx和utroin阴性肌肉中的突触，但在双突变体中缺失。因此，α-dystrobrevin-1和-2的不同分布可以部分地通过与utroin和dystrophin的特定关联来解释，但也有其他因素参与。这些结果表明，选择性剪接赋予了α-dystrobrevins不同的关联属性。
α-Dystrobrevin is both a dystrophin homologue and a component of the dystrophin protein complex. Alternative splicing yields five forms, of which two predominate in skeletal muscle: full-length α-dystrobrevin-1 (84 kD), and COOH-terminal truncated α-dystrobrevin-2 (65 kD). Using isoform-specific antibodies, we find that α-dystrobrevin-2 is localized on the sarcolemma and at the neuromuscular synapse, where, like dystrophin, it is most concentrated in the depths of the postjunctional folds. α-Dystrobrevin-2 preferentially copurifies with dystrophin from muscle extracts. In contrast, α-dystrobrevin-1 is more highly restricted to the synapse, like the dystrophin homologue utrophin, and preferentially copurifies with utrophin. In yeast two-hybrid experiments and coimmunoprecipitation of in vitro–translated proteins, α-dystrobrevin-2 binds dystrophin, whereas α-dystrobrevin-1 binds both dystrophin and utrophin. α-Dystrobrevin-2 was lost from the nonsynaptic sarcolemma of dystrophin-deficient mdx mice, but was retained on the perisynaptic sarcolemma even in mice lacking both utrophin and dystrophin. In contrast, α-dystrobrevin-1 remained synaptically localized in mdx and utrophin-negative muscle, but was absent in double mutants. Thus, the distinct distributions of α-dystrobrevin-1 and -2 can be partly explained by specific associations with utrophin and dystrophin, but other factors are also involved. These results show that alternative splicing confers distinct properties of association on the α-dystrobrevins.
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DOI：
10.1074/jbc.272.50.31561
发表时间：
1997
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Peters,MF;O'Brien,KF;Sadoulet-Puccio,HM;Kunkel,LM;Adams,ME;Froehner,SC
通讯作者：
Froehner,SC
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DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kramarcy,NR;Vidal,A;Froehner,SC;Sealock,R
通讯作者：
Sealock,R
影响因子：
3.5
作者：
Vainzof, M;PassosBueno, MR;Zatz, M
通讯作者：
Zatz, M
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影响因子：
3.5
作者：
Sadoulet-Puccio,HM;Khurana,TS;Cohen,JB;Kunkel,LM
通讯作者：
Kunkel,LM