Isoform-specific expression of the Coxsackie and adenovirus receptor (CAR) in neuromuscular junction and cardiac intercalated discs

Christian A Shaw¹ , Paul C Holland¹ , Michael Sinnreich¹ , Carol Allen¹ , Kerstin Sollerbrant² , George Karpati¹ and Josephine Nalbantoglu¹

¹Department of Neurology & Neurosurgery, McGill University and Montreal Neurological Institute, Montreal, Canada

²Ludwig Institute for Cancer Research (Stockholm Branch), Karolinska Institute, Stockholm, Sweden

author email corresponding author email

BMC Cell Biology 2004, 5:42doi:10.1186/1471-2121-5-42


Published:	8 November 2004

Abstract

Background

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.

Results

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.

Conclusion

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.