Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro

Jun Yan, Xiao Zhou, Jing-Jing Guo, Lei Mao, Yi-Jin Wang, Jing Sun, Li-Xin Sun, Lu-Yong Zhang, Xin-Fu Zhou, Hong Liao

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    52 Citations (Scopus)

    Abstract

    Nogo-66 is a 66-amino-acid-residue extracellular domain of Nogo-A, which plays a key role in inhibition neurite outgrowth of central nervous system through binding to the Nogo-66 receptor (NgR) expressed on the neuron. Recent studies have confirmed that NgR is also expressed on the surface of macrophages/microglia in multiple sclerosis, but its biological effects remain unknown. In the present study, our results demonstrated that Nogo-66 triggered microglia anti-adhesion and inhibited their migration in vitro, which was mediated by NgR. We also assessed the roles of small GTP (glycosyl phosphatidylinositol)-binding proteins of the Rho family as the downstream signal transducers on the microglia adhesion and mobility induced by Nogo-66. The results showed that Nogo-66 activated RhoA and reduced the activity of Cdc42 in the meanwhile, which further triggered the anti-adhesion and migration inhibition effects to microglia. Nogo-66 inhibited microglia polarization and membrane protrusion formation, thus might eventually contribute to the decreasing capability of cell mobility. Taken together, the Nogo-66/NgR pathway may modulate neuroinflammation via mediating microglia adhesion and migration in addition to its role in neurons. Better understanding the relationship between Nogo-66/NgR and neuroinflammation may help targeting NgR for treating central nervous system diseases related with inflammation.

    Original languageEnglish
    Pages (from-to)721-731
    Number of pages11
    JournalJournal of Neurochemistry
    Volume120
    Issue number5
    DOIs
    Publication statusPublished - 2012

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    Yan, J., Zhou, X., Guo, J-J., Mao, L., Wang, Y-J., Sun, J., Sun, L-X., Zhang, L-Y., Zhou, X-F., & Liao, H. (2012). Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro. Journal of Neurochemistry, 120(5), 721-731. https://doi.org/10.1111/j.1471-4159.2011.07619.x