title: Erbin is required for myelination in regenerated axons after injury.
abstract: Neuregulin 1 (NRG1) is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ErbB2 and ErbB3. Recent studies suggest that NRG1 signaling plays a role in remyelination of regenerated nerves after injury. In this study, we investigated the role of Erbin, a protein that interacts with ErbB2 in remyelination of injured nerves. We show that Erbin expression increased dramatically in injured nerves. Myelinated axons were fewer, and g-ratios of those that were myelinated were increased in erbin(-/-) mice, which were impaired in functional recovery from nerve injury. These results indicate a necessary role of Erbin in remyelination of regenerating axons. Erbin ablation had little effect on numbers of BrdU-labeled and TUNEL-labeled SCs, suggesting mechanisms independent of altered proliferation or apoptosis. We demonstrated that Erbin mutant mice were impaired in raising or maintaining the levels of ErbB2 and in producing NRG1 in axons. Together, these observations demonstrate that Erbin is required for remyelination of regenerated axons after injury, probably by regulating ErbB2 and NRG1 levels, identifying a novel player in regulating remyelination.
authors.affiliation: Institute of Molecular Medicine and Genetics and Department of Neurology, Georgia Health Science University, Augusta, Georgia 30912, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liang
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Tao
authors.forename: Chengyong
authors.initials: C
authors.lastname: Shen
authors.forename: Zui
authors.initials: Z
authors.lastname: Tan
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001973:Bromodeoxyuridine; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D020890:Neuregulin-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology; D020426:Sciatic Neuropathy / Q000150:complications / Q000473:pathology*; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D004676:Myelin Basic Protein; D020890:Neuregulin-1; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C498804:Erbb2ip protein, mouse; C490581:Nrg1 protein, mouse; C524056:Erbb2 protein, mouse