Myospryn is a novel binding partner for dysbindin in muscle
Myospryn is a novel binding partner for dysbindin in muscle
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DOI：
10.1074/jbc.m312664200
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发表时间：
2004-03-12
影响因子：
4.8
通讯作者：
Blake, DJ
中科院分区：
文献类型：
--
作者：
Benson, MA;Tinsley, CL;Blake, DJ
Dybindin是一种含有螺旋卷曲的蛋白质，最初是在dystrobrevin相互作用蛋白的筛查中发现的。最近研究表明，dybindin参与了溶酶体相关细胞器的生物发生，也是精神分裂症的一个主要易感因素。虽然异常结合蛋白与许多不同的细胞过程有关，但人们对其功能知之甚少。为了确定异常结合蛋白在肌肉中的功能，我们进行了酵母双杂交筛选，以确定潜在的相互作用蛋白。在这里，我们显示了dybindin与一种新的413 kDa的蛋白myospryn结合，该蛋白在心肌和骨骼肌中表达。编码myospryn的转录本包括染料乙素-3，这是一种在Duchenne肌营养不良症患者肌肉中下调的转录本，以及拉伸反应蛋白553，它在实验性肌肉肥大中上调。Myospryn的C末端含有BBC、FN3和SPRY结构域，其结构使人想起三方基序蛋白家族，以及异常结合位点和介导自结合的区域。Dybindin和myospryn从肌肉提取物中免疫共沉淀，并广泛共存。这些数据首次表明，在涉及该蛋白的不同疾病状态中，可能有组织特异性结合蛋白配体发挥重要作用。
Dysbindin is a coiled-coil-containing protein that was initially identified in a screen for dystrobrevin-interacting proteins. Recently, dysbindin has been shown to be involved in the biogenesis of lysosome-related organelles and is also a major schizophrenia susceptibility factor. Although dysbindin has been implicated in a number of different cellular processes, little is known about its function. To determine the function of dysbindin in muscle, we performed a yeast two-hybrid screen to identify potential interacting proteins. Here we show that dysbindin binds to a novel 413-kDa protein, myospryn, which is expressed in cardiac and skeletal muscle. The transcript encoding myospryn encompasses genethonin-3, a transcript that is down-regulated in muscle from Duchenne muscular dystrophy patients and stretch-responsive protein 553, which is up-regulated in experimental muscle hypertrophy. The C terminus of myospryn contains BBC, FN3, and SPRY domains in a configuration reminiscent of the tripartite motif protein family, as well as the dysbindin-binding site and a region mediating self-association. Dysbindin and myospryn co-immunoprecipitate from muscle extracts and are extensively co-localized. These data demonstrate for the first time that there are tissue-specific ligands for dysbindin that may play important roles in the different disease states involving this protein.