Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease

• Type of Material: Article
• Authors: Samuel M. Lee, Emory University; Lih-Shen Chin, Emory University; Lian Li, Emory University
• Language: English
• Date: 2017-01-01
• Publisher: Humana Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Springer Science+Business Media New York.
• Final Published Version (URL): http://dx.doi.org/10.1007/s12035-015-9668-2
• Title of Journal or Parent Work: Molecular Neurobiology
• ISSN: 0893-7648
• Volume: 54
• Issue: 1
• Start Page: 87
• End Page: 100
• Grant/Funding Information: The authors’ research is supported by National Institutions of Health (NIH) grants NS063501 (S.M.L.), NS093550 (L.S.C.), GM103613, and NS092343 (L.L.).
• Keywords: Endocytic trafficking; Life Sciences & Biomedicine; NERVOUS-SYSTEM; CANCER THERAPEUTICS; ESCRT MACHINERY; DOMAIN PROTEIN; MISSENSE MUTATIONS; GROWTH-FACTOR RECEPTOR; SOLUBLE NEUREGULIN-1; Neurosciences & Neurology; ENDOSOMAL TRAFFICKING; Charcot-Marie-Tooth disease; SCHWANN-CELL MYELINATION; Peripheral neuropathy; ErbB receptor; MOUSE MODEL; Science & Technology; Demyelination; Neurosciences
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy.