Utrophin: A structural and functional comparison to dystrophin
Utrophin: A structural and functional comparison to dystrophin
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DOI：
10.1111/j.1750-3639.1996.tb00781.x
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发表时间：
1996-01-01
期刊：
影响因子：
6.4
通讯作者：
Davies, KE
中科院分区：
文献类型：
--
作者：
Blake, DJ;Tinsley, JM;Davies, KE
肌营养不良蛋白是肌营养不良蛋白的常染色体编码同源物，肌营养不良蛋白是杜氏肌营养不良（DMD）基因的蛋白产物。虽然肌营养不良蛋白在序列上与肌营养不良蛋白非常相似，并且具有归因于肌营养不良蛋白的许多蛋白质结合特性，但是这两种蛋白质以明显相互的方式表达，并且可以协同调节。在正常骨骼肌中，肌营养不良蛋白存在于神经肌肉接头（NMJ），而肌营养不良蛋白主要存在于肌膜。然而，在发育过程中，以及在一些肌病包括DMD中，肌营养蛋白也在肌膜中发现。这种再分布通常与utrophin水平的显著增加相关。在NMJ，utrophin与乙酰胆碱受体（AChR）共定位，并且可能在突触细胞骨架的稳定中起作用。由于肌营养不良蛋白和肌营养不良蛋白是如此相似，肌营养不良蛋白可能能够取代肌营养不良蛋白缺乏的肌肉。这篇综述比较了utrophin的结构和功能，肌营养不良蛋白，并讨论了使用utrophin作为一个潜在的治疗剂背后的基本原理。
Utrophin is an autosomally-encoded homologue of dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene. Although, utrophin is very similar in sequence to dystrophin and possesses many of the protein-binding properties ascribed to dystrophin, both proteins are expressed in an apparently reciprocal manner and may be coordinately regulated. In normal skeletal muscle, utrophin is found at the neuromuscular junction (NMJ) whereas dystrophin predominates at the sarcolemma. However, during development, and in some myopathies including DMD, utrophin is also found at the sarcolemma. This re-distribution is often associated with a significant increase in the levels of utrophin. At the NMJ utrophin co-localizes with the acetylcholine receptors (AChR) and may play a role in the stabilization of the synaptic cytoskeleton. Because utrophin and dystrophin are so similar, utrophin may be able to replace dystrophin in dystrophin deficient muscle. This review compares the structure and function of utrophin to dystrophin and discusses the rationale behind the use of utrophin as a potential therapeutic agent.