title: LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.
abstract: Oligodendrocyte differentiation is negatively regulated by LINGO-1 and positively regulated by the ErbB2 receptor tyrosine kinase. In wild-type oligodendrocytes, inhibition of ErbB2 blocks differentiation, whereas activation of ErbB2 promotes differentiation. In LINGO-1(-/-) oligodendrocytes, inhibition of ErbB2 blocks oligodendrocyte differentiation; whereas activation of ErbB2 does not enhance differentiation. Biological and biochemical evidence showing that LINGO-1 can directly bind to ErbB2, block ErbB2 translocation into lipid rafts, and inhibit its phosphorylation for activation. The study demonstrates a novel regulatory mechanism of ErbB2 function whereby LINGO-1 suppresses oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. Electronic address: xinhua.lee@biogenidec.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lee
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. Electronic address: zhaohui.shao@biogenidec.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. Electronic address: guoqing.sheng@biogenidec.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Sheng
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. Electronic address: blake.pepinsky@biogenidec.com.
authors.forename: Blake
authors.initials: B
authors.lastname: Pepinsky
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. Electronic address: sha.mi@biogenidec.com.
authors.forename: Sha
authors.initials: S
authors.lastname: Mi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C482293:LINGO1 protein, human; C508053:ERBB2 protein, human
keywords: ErbB2; LINGO-1; Lipid raft; Multiple sclerosis; Oligodendrocyte