title: Anti-GM1 antibodies affect the integrity of lipid rafts.
abstract: Previous studies have shown that patients with the axonal form of Guillain-Barré syndrome (GBS) develop autoantibodies against GM1 ganglioside (GM1). Nerve growth factor (NGF) is essential for neuronal survival in vivo and its functional receptor is Trk-tyrosine kinase. Here, we examined the biological effects of sera from patients with the axonal form of GBS on the morphology and the phosphorylation state of Trk-tyrosine kinase in PC12 cells. Furthermore, we examined the effect of the sera on the integrity of membrane lipid rafts biochemically. The data show that anti-GM1 antibodies found in patients' sera but not control sera inhibit NGF-induced Trk autophosphorylation. Most intriguingly, the autoantibodies alter the distribution of Trk in lipid rafts without shifting the distribution of a rafts marker protein. These data strongly suggest that anti-GM1 antibodies directly influence the integrity of the signaling platform, lipid rafts, implicating the importance of lipid rafts in the development of this disorder.
authors.affiliation: The Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ueda
authors.forename: Sayuri
authors.initials: S
authors.lastname: Shima
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Miyashita
authors.forename: Shinji
authors.initials: S
authors.lastname: Ito
authors.forename: Masami
authors.initials: M
authors.lastname: Ueda
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Asakura
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D005677:G(M1) Ganglioside; D020932:Nerve Growth Factor; D020917:Receptor, trkA