TACE cleaves neogenin to desensitize cortical neurons to the repulsive guidance molecule |
| |
Authors: | Okamura Yusuke Kohmura Eiji Yamashita Toshihide |
| |
Affiliation: | a Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan b Department of Neurosurgery, Graduate School of Medicine, Kobe University, Kobe, Japan c JST, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan |
| |
Abstract: | Neogenin is a receptor for netrins and proteins of the repulsive guidance molecule (RGM) family. It regulates several key developmental processes within the nervous system. The binding of RGMa to neogenin induces the inhibition of neurite outgrowth and the collapse of the growth cone of neurons. Here, we report that a disintegrin and metalloprotease (ADAM) transmembrane protein regulates the sensitivity of neurons to RGMa, by inducing the shedding of the ectodomain of neogenin. The extracellular domain of neogenin is directly associated with and cleaved off by the tumor necrosis factor-α converting enzyme (TACE), also called ADAM17. TACE is endogenously expressed in embryonic cortical neurons and regulates the cleavage of neogenin, and the inhibition of TACE in turn enhances RGMa-induced inhibition of neurite outgrowth and collapse of the growth cone. Conversely, exogenous expression of TACE abolishes the effect of RGMa. Therefore, TACE may play a role in modulating the RGM-induced repulsive behavior of neurons by regulating the expression of neogenin on the cell surface. |
| |
Keywords: | TACE Neogenin Neurons Sheddase Receptor |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|