Shaw Christian A, Holland Paul C, Sinnreich Michael, Allen Carol, Sollerbrant Kerstin, Karpati George, Nalbantoglu Josephine
Department of Neurology & Neurosurgery, McGill University and Montreal Neurological Institute, Montreal, Canada.
BMC Cell Biol. 2004 Nov 8;5(1):42. doi: 10.1186/1471-2121-5-42.
The Coxsackie and adenovirus receptor (CAR) has a restricted expression pattern in the adult. In skeletal muscle, although CAR is expressed in immature fibers, its transcript levels are barely detectable in mature muscle. This is in contrast to the robust expression observed in the heart. However, both heart and skeletal muscle are susceptible to infection with the Coxsackie B virus which utilizes primarily CAR for cellular internalization. The specific point of viral entry in skeletal and heart muscle remains unknown.
Using antibodies directed against the extracellular and the cytoplasmic domains of CAR, we show CAR in normal human and mouse skeletal muscle to be a novel component of the neuromuscular junction. In cardiac muscle, CAR immunoreactivity is observed at the level of intercalated discs. We demonstrate a single isoform of CAR to be expressed exclusively at the human neuromuscular junction whereas both predominant CAR isoforms are expressed at the intercalated discs of non-diseased human heart.
The localization of CAR to these important junctional complexes suggests that CAR may play both a structural and a regulatory role in skeletal and cardiac muscle, and that these complexes may serve as a point of entry for Coxsackie B virus.
柯萨奇病毒和腺病毒受体（CAR）在成体中具有受限的表达模式。在骨骼肌中，尽管CAR在未成熟纤维中表达，但其转录水平在成熟肌肉中几乎检测不到。这与在心脏中观察到的强烈表达形成对比。然而，心脏和骨骼肌都易受柯萨奇B病毒感染，该病毒主要利用CAR进行细胞内化。病毒在骨骼肌和心肌中的具体进入点仍然未知。
使用针对CAR细胞外和细胞质结构域的抗体，我们发现正常人和小鼠骨骼肌中的CAR是神经肌肉接头的一种新成分。在心肌中，在闰盘水平观察到CAR免疫反应性。我们证明在人类神经肌肉接头处仅表达一种CAR异构体，而在未患病的人类心脏闰盘中表达两种主要的CAR异构体。
CAR定位于这些重要的连接复合体表明，CAR可能在骨骼肌和心肌中发挥结构和调节作用，并且这些复合体可能是柯萨奇B病毒的进入点。
