DMPK PROTEIN ISOFORMS ARE DIFFERENTIALLY EXPRESSED IN MYOGENIC AND NEURAL CELL LINEAGES
DMPK PROTEIN ISOFORMS ARE DIFFERENTIALLY EXPRESSED IN MYOGENIC AND NEURAL CELL LINEAGES
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DOI：
10.1002/mus.21352
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发表时间：
2009-10-01
期刊：
影响因子：
3.4
通讯作者：
Wansink, Derick G.
中科院分区：
文献类型：
--
作者：
Oude Ophuis, Ralph J. A.;Mulders, Susan A. M.;Wansink, Derick G.
强直性肌营养不良1型（DM 1）是一种神经肌肉疾病引起的不稳定（CTG。CAG）n片段。人们普遍认为，DMPK mRNA为基础的毒性是DM 1表现的主要贡献者;然而，对DMPK蛋白的意义知之甚少。为了了解其正常和可能的病理生物学作用，我们分析了DMPK剪接异构体在小鼠组织中的表达模式。长膜锚定DMPK占主导地位的心脏，膈肌和骨骼肌，而短胞质异构体在膀胱和胃中高度表达。这两种亚型存在于不同的脑区。DMPK蛋白在培养的成肌细胞、肌管、皮质星形胶质细胞和神经或肌肉来源的相关细胞系中也可检测到，但在海马神经元中未检测到。这项工作将DMPK鉴定为在DM 1中受影响的各种肌肉和神经组织中具有显著表达的激酶。肌肉神经40：545-555，2009
Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by an unstable (CTG . CAG)n segment in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. It is commonly accepted that DMPK mRNA-based toxicity is the main contributor to DM1 manifestations; however, not much is known about the significance of the DMPK protein. To appreciate its normal and possible pathobiological role, we analyzed the patterns of DMPK splice isoform expression in mouse tissues. Long membrane-anchored DMPK dominated in heart, diaphragm, and skeletal muscle, whereas short cytosolic isoforms were highly expressed in bladder and stomach. Both isoform types were present in diverse brain regions. DMPK protein was also detectable in cultured myoblasts, myotubes, cortical astrocytes, and related cell lines of neural or muscle origin, but not in hippocampal neurons. This work identifies DMPK as a kinase with pronounced expression in diverse muscle and neural tissues that are affected in DM1. Muscle Nerve 40: 545-555, 2009