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Nogo‐66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro
Author(s) -
Yan Jun,
Zhou Xiao,
Guo JingJing,
Mao Lei,
Wang YiJin,
Sun Jing,
Sun LiXin,
Zhang LuYong,
Zhou XinFu,
Liao Hong
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07619.x
Subject(s) - microglia , neurite , neuroinflammation , rhoa , microbiology and biotechnology , gtpase , cdc42 , chemistry , semaphorin , receptor , in vitro , neuroscience , biology , signal transduction , inflammation , immunology , biochemistry
J. Neurochem. (2012) 120 , 721–731. 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.