title: Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro.
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.
authors.affiliation: Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Mao
authors.forename: Yi-Jin
authors.initials: YJ
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Sun
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins