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Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site.
Tang, S; Shen, Y J; DeBellard, M E; Mukhopadhyay, G; Salzer, J L; Crocker, P R; Filbin, M T.
Afiliação
  • Tang S; Department of Biological Sciences, Hunter College of the City University of New York 10021, USA.
J Cell Biol ; 138(6): 1355-66, 1997 Sep 22.
Article em En | MEDLINE | ID: mdl-9298990
Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid-dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid- dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid-dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neuritos / Glicoproteína Associada a Mielina / Ácido N-Acetilneuramínico / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 1997 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neuritos / Glicoproteína Associada a Mielina / Ácido N-Acetilneuramínico / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 1997 Tipo de documento: Article