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Neuregulin Receptor ErbB2 Localization at T-tubule in Cardiac and Skeletal Muscle

Hideho Ueda, Akihiro Oikawa, Akinori Nakamura, Fumiko Terasawa, Kyutaro Kawagishi and Tetsuji Moriizumi

Departments of Anatomy and Cell Biology (HU,AO) and Biomedical Laboratory Sciences (FT), School of Health Sciences, Shinshu University, Nagano, Japan, and 3rd Department of Internal Medicine (AN) and Department of Anatomy (KK,TM), Shinshu University School of Medicine, Nagano, Japan

Correspondence to: Hideho Ueda, MD, PhD, Department of Anatomy and Cell Biology, School of Health Sciences, Shinshu University, Matsumoto, Nagano 390-8621, Japan. E-mail: hueda{at}gipac.shinshu-u.ac.jp

Previous studies have indicated that ErbB receptors for neuregulins play an important role in cardiac development and muscle spindle formation during embryogenesis; however, little is known about their functions in adulthood. Recent reports indicate that breast cancer therapy with humanized monoclonal ErbB2 antibody induces cardiomyopathy, suggesting that ErbB2 serves as a crucial signaling receptor, even in the adult heart. Here, we examine ErbB2 expression and localization in both cardiac and skeletal muscle of adult mice via immunoblot and immunohistochemistry. ErbB2 was detected as a band 185 kD molecular mass in each cardiac and skeletal muscle extraction. Confocal images of double labeling showed that ErbB2 was colocalized with caveolin-3 in cardiac muscle and with dihydropyridine receptor in skeletal muscle, suggesting that ErbB2 was localized at the T-tubule. In addition, immunoelectron micrographs clearly demonstrated that ErbB2 was located at the T-tubule in both types of muscle. Taken together, the results of the present study suggest that neuregulin-ErbB2 signaling plays a role in the physiological function of cardiac and skeletal muscle, even in adulthood.

(J Histochem Cytochem 53:87–91, 2005)

Key Words: ErbB2 • neuregulin • cardiac muscle • skeletal muscle • T-tubule

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