Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro
Article first published online: 23 JAN 2012
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 120, Issue 5, pages 721–731, March 2012
How to Cite
Yan, J., Zhou, X., Guo, J.-J., Mao, L., Wang, Y.-J., Sun, J., Sun, L.-X., Zhang, L.-Y., Zhou, X.-F. and Liao, H. (2012), Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in vitro. Journal of Neurochemistry, 120: 721–731. doi: 10.1111/j.1471-4159.2011.07619.x
- Issue published online: 10 FEB 2012
- Article first published online: 23 JAN 2012
- Accepted manuscript online: 7 DEC 2011 07:12AM EST
- Received October 29, 2011; revised manuscript received November 29, 2011; accepted November 29, 2011.
J. Neurochem. (2012) 120, 721–731.
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.