LINGO family receptors are differentially expressed in the mouse brain and form native multimeric complexes

Leucine‐rich repeat and immunoglobin‐domain containing (LRRIG) proteins that are commonly involved in protein‐protein interactions play important roles in nervous system development and maintenance. LINGO‐1, one of this family members, is characterized as a negative regulator of neuronal survival, a...

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Published in:The FASEB journal 2020-10, Vol.34 (10), p.13641-13653
Main Authors: Guillemain, Anthony, Laouarem, Yousra, Cobret, Laetitia, Štefok, Dora, Chen, Wanyin, Bloch, Solal, Zahaf, Amina, Blot, Lauren, Reverchon, Flora, Normand, Thierry, Decoville, Martine, Grillon, Catherine, Traiffort, Elisabeth, Morisset‐Lopez, Séverine
Format: Article
Language:English
Subjects:
Animals
Biochemistry, Molecular Biology
Brain - metabolism
BRET
HEK293 Cells
Humans
Life Sciences
LRRIG
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Molecular biology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
nervous system
oligomerization
Protein Binding
Protein Multimerization
protein‐protein interactions
transmembrane protein
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Summary:Leucine‐rich repeat and immunoglobin‐domain containing (LRRIG) proteins that are commonly involved in protein‐protein interactions play important roles in nervous system development and maintenance. LINGO‐1, one of this family members, is characterized as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte precursor cell (OPC) differentiation into mature myelinating oligodendrocytes. Three LINGO‐1 homologs named LINGO‐2, LINGO‐3, and LINGO‐4 have been described. However, their relative expression and functions remain unexplored. Here, we show by in situ hybridization and quantitative polymerase chain reaction that the transcripts of LINGO homologs are differentially expressed in the central nervous system. The immunostaining of brain slices confirmed this observation and showed the co‐expression of LINGO‐1 with its homologs. Using BRET (bioluminescence resonance energy transfer) analysis, we demonstrate that LINGO proteins can physically interact with each of the other ones with comparable affinities and thus form the oligomeric states. Furthermore, co‐immunoprecipitation experiments indicate that LINGO proteins form heterocomplexes in both heterologous systems and cortical neurons. Since LINGO‐1 is a promising target for the treatment of demyelinating diseases, its ability to form heteromeric complexes reveals a new level of complexity in its functioning and opens the way for new strategies to achieve diverse and nuanced LINGO‐1 regulation.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202000826R