LINGO-1 protein interacts with the p75 neurotrophin receptor in intracellular membrane compartments.

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.
Mesh Terms:
Animals, Animals, Newborn, Binding, Competitive, Brain, Cell Membrane, GPI-Linked Proteins, HEK293 Cells, Humans, Immunoblotting, Immunoprecipitation, Intracellular Membranes, Membrane Proteins, Mice, Inbred C57BL, Microscopy, Confocal, Mutation, Myelin Proteins, Nerve Tissue Proteins, Neurons, Nogo Receptor 1, Polysaccharides, Protein Binding, Receptors, Cell Surface, Receptors, Nerve Growth Factor
J. Biol. Chem.
Date: Apr. 10, 2015
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