Investigations on the cellular and neuroprotective functions of Nogo-A/Reticulon 4A

Abstract

Nogo/RTN4 is a member of the Reticulon (RTN) family and is first discovered as a myelin-associated inhibitor that inhibits neurite outgrowth. Our Nogo-A (the longest isoform) specific antibodies showed that it is enriched in the CNS, where its expression is found in both oligodendrocytes and neurons. Presence of Nogo-A in the former may be expected because of its inhibitory activity, but its presence in neurons is surprising. We found Nogo-A enriched at the axon-glial junction at the paranode, where it is able to interact with the neuronal Caspr/paranodin. Nogo-A also interacts with the brain-enriched RTN3 via the reticulon homology domain. Neuronal Nogo-A expression is elevated during injury, and may function as part of the neuron?s injury response and survival mechanism. When overexpressed in neuroblastoma cells, Nogo-A protects against various modes of cell death, possibly via a complex suite of mechanisms.