MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth |
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Authors: | Domeniconi Marco Zampieri Niccolò Spencer Tim Hilaire Melissa Mellado Wilfredo Chao Moses V Filbin Marie T |
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Affiliation: | Biology Department, Hunter College, City University of New York, 695 Park Avenue, New York, New York 10021, USA. |
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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. |
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