From Cell Death to Neuronal Regeneration, Effects of the p75 Neurotrophin Receptor Depend on Interactions with Partner Subunits

In the adult mammalian central nervous system (CNS), growth of neuronal fibers is actively inhibited by myelin. The proteins myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgP), and Nogo-66 have been identified as inhibitory components present in CNS myelin. All three proteins exert their inhibitory activity by binding to a neuronal receptor complex containing the Nogo-66 receptor (NgR) and the neurotrophin (NT) receptor p75NTR. In their recent publication, Mi et al. identify the novel protein Lingo-1 as an interactor of p75NTR and NgR. The Lingo-1-NgR-p75NTR complex is shown to confer the inhibitory effects on nerve cell regeneration of Nogo-66, OMgP, and MAG by activating the small guanosine triphosphatase (GTPase) RhoA. Together with the recent finding that p75NTR interacts with the transmembrane protein sortilin to form a different receptor complex with cell death-promoting activity, the results of Mi et al. indicate that p75NTR exerts its diverse cellular functions by associating with function-specific co-receptors.