TACE‐induced cleavage of Neogenin disinhibits CNS axon/neurite growth by RGM in rat primary cortical neuron

Abstract

Neogenin is multifunctional receptor implicated in axon navigation, neuronal differentiation, morphogenesis, and cell death. Recently, neogenin appears to be a high‐affinity receptor for the repulsive guidance molecule (RGM), and RGMa‐neogenin interaction inhibits axon regeneration. While performing a two‐hybrid screen using the intracellular domain of neogenin, we observed that neogenin bound to ADAM17, also called TACE (TNF‐alpha converting enzyme). TACE is a 70‐kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases, and plays a role in proteolytic processing of some kinds of receptors, ligands, and enzymes. This process is of physiological importance. We show here that the cleavage of neogenin by TACE attenuates RGMa‐dependent neurite outgrowth inhibition in rat primary cortical neuron. Thus, TACE can be used as a molecular target for clinical conditions characterized by a failure of CNS regeneration