Journal Article

LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex

Allaire, Norm, Sands, Bryan, Ji, Benxiu, Lee, Xinhua, Levesque, Melissa, Shao, Zhaohui, Crowell, Thomas, Mi, Sha, McCoy, John M, Relton, Jane, Pepinsky, R Blake, Perrin, Steve, Thill, Greg, Cate, Richard L

2004

Overview

Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These inhibitors seem to modulate RhoA activity by binding to a receptor complex comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal transducing subunit (the neurotrophin receptor p75). However, in reconstituted non-neuronal systems, NgR1 and p75 together are unable to activate RhoA, suggesting that additional components of the receptor may exist. Here we describe LINGO-1, a nervous system-specific transmembrane protein that binds NgR1 and p75 and that is an additional functional component of the NgR1/p75 signaling complex. In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA activation. A dominant-negative human LINGO-1 construct attenuated myelin inhibition in transfected primary neuronal cultures. This effect on neurons was mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together these observations suggest that LINGO-1 has an important role in CNS biology.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Amino Acid Sequence - genetics / Animal Genetics and Genomics / Animals / Animals, Newborn / Astrocytes - metabolism / Axons - metabolism / Base Sequence - genetics / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Cells, Cultured / DNA, Complementary - analysis / DNA, Complementary - genetics / Fetus / GPI-Linked Proteins / Humans / LINGO-1 protein / Macromolecular Substances / Membrane Proteins - genetics / Membrane Proteins - isolation & purification / Membrane Proteins - metabolism / Molecular Sequence Data / Mutation - genetics / Myelin Proteins - metabolism / Myelin Sheath - metabolism / Myelin-Associated Glycoprotein - genetics / Myelin-Associated Glycoprotein - isolation & purification / Myelin-Associated Glycoprotein - metabolism / Myelin-Oligodendrocyte Glycoprotein / Nerve Regeneration - physiology / Nerve Tissue Proteins / Neurobiology / Neurosciences / Nogo Receptor 1 / Nogo receptors / Pharmaceutical industry / Protein Structure, Tertiary - genetics / Rats / Receptor, Nerve Growth Factor / Receptors, Cell Surface - genetics / Receptors, Cell Surface - isolation & purification / Receptors, Cell Surface - metabolism / Receptors, Nerve Growth Factor - metabolism / Recombinant Fusion Proteins - genetics / Recombinant Fusion Proteins - metabolism / rhoA GTP-Binding Protein - metabolism / RhoA protein / Signal Transduction - genetics