title: LINGO-1 protein interacts with the p75 neurotrophin receptor in intracellular membrane compartments.
abstract: Axon outgrowth inhibition in response to trauma is thought to be mediated via the binding of myelin-associated inhibitory factors (e.g. Nogo-66, myelin-associated glycoprotein, oligodendrocyte myelin glycoprotein, and myelin basic protein) to a putative tripartite LINGO-1·p75(NTR)·Nogo-66 receptor (NgR) complex at the cell surface. We found that endogenous LINGO-1 expression in neurons in the cortex and cerebellum is intracellular. Mutation or truncation of the highly conserved LINGO-1 C terminus altered this intracellular localization, causing poor intracellular retention and increased plasma membrane expression. p75(NTR) associated predominantly with natively expressed LINGO-1 containing immature N-glycans, characteristic of protein that has not completed trans-Golgi-mediated processing, whereas mutant forms of LINGO-1 with enhanced plasma membrane expression did not associate with p75(NTR). Co-immunoprecipitation experiments demonstrated that LINGO-1 and NgR competed for binding to p75(NTR) in a manner that is difficult to reconcile with the existence of a LINGO-1·p75(NTR)·NgR ternary complex. These findings contradict models postulating functional LINGO-1·p75(NTR)·NgR complexes in the plasma membrane.
authors: From the Departments of Psychiatry and Behavioral Sciences, the Mental Illness Research Education and Clinical Center, Veterans Affairs Medical Center, Seattle, Washington 98108.
authors: James S
authors: JS
authors: Meabon
authors: Immusoft, Seattle, Washington 98103, and.
authors: Rian
authors: R
authors: De Laat
authors: the Department of Pharmacology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
authors: Katsuaki
authors: K
authors: Ieguchi
authors: Comparative Medicine, and.
authors: Jesse C
authors: JC
authors: Wiley
authors: Physiology and Biophysics, University of Washington, Seattle, Washington 98195.
authors: Mark P
authors: MP
authors: Hudson
authors: Physiology and Biophysics, University of Washington, Seattle, Washington 98195, mab@uw.edu.
authors: Mark
authors: M
authors: Bothwell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D000070816:Nogo Receptor 1; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009185:Myelin Proteins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D011134:Polysaccharides; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor
keywords: Cell Surface; Endosome; Golgi; LINGO-1; NgR; Nogo Receptor; Vesicles; p75 Neurotrophin Receptor