Phosphorylation of Nogo Receptors Suppresses Nogo Signaling, Allowing Neurite Regeneration

The myelin-associated proteins Nogo-A, MAG, and OMgp transmit signals from oligodendrocytes into neurons through binding to Nogo receptors. Nogo signaling has critical roles in development and maintenance of the central nervous system (CNS). It can inhibit differentiation, migration, and neurite outgrowth of neurons, causing poor recovery of the adult CNS from damage. Here, I show that phosphorylation of Nogo receptors by casein kinase II (CK2) inhibits binding of the myelin-associated proteins. Brain-derived neurotrophic factor stimulates the phosphorylation, suppressing Nogo-dependent inhibition of neurite outgrowth from neuroblastoma-derived neural cells. Similarly, in rat adult neurons, extracellular CK2 treatment overcomes inhibition of neurite outgrowth by the myelin-associated proteins. These findings provide new strategies to control Nogo signaling and hence neuronal regeneration.