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¹ Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
² Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan

Address correspondence to Toshihide Yamashita, Dept. of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-68793221. Fax: 81-6-68793229. E-mail: tyama{at}anat2.med.osaka-u.ac.jp

Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The receptor for MAG or signals that elicit morphological changes in neurons remained to be established. Here we show that the neurotrophin receptor p75 (p75^NTR) is the signal transducing element for MAG. Adult dorsal root ganglion neurons or postnatal cerebellar neurons from mice carrying a mutation in the p75^NTR gene are insensitive to MAG with regard to neurite outgrowth. MAG activates small GTPase RhoA, leading to retarded outgrowth when p75^NTR is present. Colocalization of p75^NTR and MAG binding is seen in neurons. Ganglioside GT1b, which is one of the binding partners of MAG, specifically associates with p75^NTR. Thus, p75^NTR and GT1b may form a receptor complex for MAG to transmit the inhibitory signals in neurons.

Key Words: p75; neurotrophin; myelin-associated glycoprotein; Rho; ganglioside

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