An in vitro study on the involvement of LINGO-1 and Rho GTPases in Nogo-A regulated differentiation of oligodendrocyte precursor cells.
Nogo-A has been considered as one of the most important myelin-associated axonal regeneration inhibitors in the central nervous system. Recent studies have demonstrated various additional physiological roles of Nogo family members. To understand the possible effect of Nogo-A on the differentiation of oligodendrocytes, antibodies against distinct extracellular domains of Nogo-A were applied in cell cultures. Oligodendrocyte precursor cells from P2 rat cortex were grown in the presence of monoclonal antibody against the N-terminal inhibitory domain of Nogo-A or the C-terminal 66 amino acid loop of Nogo-A for 3 days, and the antibody treatment resulted in stunted process extension and inhibited differentiation of oligodendrocytes. Concomitant with morphology changes, Rho GTPases activity was greatly increased upon the antibody treatment and the expression level of LINGO-1, which was recently shown to be a negative regulator for the oligodendrocyte maturation, was upregulated in the process of antibody treatment. These results indicate that endogenous Nogo-A expressed in oligodendrocyte may act though Rho GTPase and LINGO-1 to influence the morphological differentiation of oligodendrocytes and will help us to understand the physiology role of Nogo-A in oligodendrocyte biology.
Zhao
Xiang-Hui
XH
Institute of Neurosciences, The Fourth Military Medical University, 17 Chang Le Xi Road, 710032 Xi 'an, PR China.
Jin
Wei-Lin
WL
Ju
Gong
G
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay; D005732:Gangliosides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000502:physiology; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D008565:Membrane Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D012333:RNA, Messenger; C000603197:Rtn4 protein, rat; C062875:ganglioside A2B5; D020741:rho GTP-Binding Proteins