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Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Published on: October 15, 2014
Neuregulin receptor ErbB2 localization at T-tubule in cardiac and skeletal muscle
Hideho Ueda1, Akihiro Oikawa, Akinori Nakamura
1Department of Anatomy and Cell Biology, School of Health Sciences, Shinshu University, Matsumoto, Nagano 390-8621, Japan. hueda@gipac.shinshu-u.ac.jp
Abstract:
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 approximately 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.
Insights
The ErbB2 receptor is present in adult cardiac and skeletal muscles, specifically at the T-tubule. This suggests neuregulin-ErbB2 signaling is vital for adult muscle physiological function.
Area of Science:
- Physiology
- Molecular Biology
- Cardiovascular Science
Background:
- ErbB receptors for neuregulins are crucial for embryonic development.
- Their function in adult cardiac and skeletal muscle remains largely unknown.
- ErbB2 signaling is implicated in adult heart function due to breast cancer therapy side effects.
Purpose of the Study:
- To investigate the expression and localization of ErbB2 in adult mouse cardiac and skeletal muscle.
- To determine the role of neuregulin-ErbB2 signaling in adult muscle physiology.
Main Methods:
- Immunoblotting to detect ErbB2 protein.
- Immunohistochemistry and confocal microscopy for localization studies.
- Immunoelectron microscopy for high-resolution structural analysis.
Main Results:
- ErbB2 protein (approx. 185 kD) was detected in both cardiac and skeletal muscle extracts.
- ErbB2 colocalized with caveolin-3 in cardiac muscle and dihydropyridine receptor in skeletal muscle.
- ErbB2 was definitively localized to the T-tubule in both muscle types.
Conclusions:
- ErbB2 is expressed and localized at the T-tubule in adult cardiac and skeletal muscles.
- Neuregulin-ErbB2 signaling likely plays a role in the physiological functions of adult muscles.
- Further research into this signaling pathway could reveal new therapeutic targets for muscle disorders.
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