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MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth

Item Type:Article
Title:MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth
Creators Name:Domeniconi, M. and Zampieri, N. and Spencer, T. and Hilaire, M. and Mellado, W. and Chao, M.V. and Filbin, M.T.
Abstract:The three known inhibitors of axonal regeneration present in myelin-MAG, Nogo, and OMgp-all interact with the same receptor complex to effect inhibition via protein kinase C (PKC)-dependent activation of the small GTPase Rho. The transducing component of this receptor complex is the p75 neurotrophin receptor. Here we show that MAG binding to cerebellar neurons induces alpha- and then gamma-secretase proteolytic cleavage of p75, in a protein kinase C-dependent manner, and that this cleavage is necessary for both activation of Rho and inhibition of neurite outgrowth.
Keywords:Amyloid Precursor Protein Secretases, Aspartic Acid Endopeptidases, Cerebellum, Cultured Cells, Drug Interactions, Endopeptidases, Enzyme Activation, Enzyme Inhibitors, Membrane Proteins, Myelin-Associated Glycoprotein, Nerve Growth Factor Receptor, Nerve Growth Factor Receptors , Neural Inhibition, Neurites, Neuroblastoma, Neurons, Recombinant Fusion Proteins, rho GTP-Binding Proteins, Tertiary OligopeptidesProtein Structure, Tetradecanoylphorbol Acetate, Transfection, Western Blotting, Animals, Cricetinae, Cricetulus, Rats
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press (U.S.A.)
Volume:46
Number:6
Page Range:849-855
Date:16 June 2005
Official Publication:https://doi.org/10.1016/j.neuron.2005.05.029
PubMed:View item in PubMed

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