LINGO family receptors are differentially expressed in the mouse brain and form native multimeric complexes.
BRET
LRRIG
nervous system
oligomerization
protein-protein interactions
transmembrane protein
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
07
04
2020
revised:
10
07
2020
accepted:
29
07
2020
pubmed:
31
8
2020
medline:
1
5
2021
entrez:
31
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32862444
doi: 10.1096/fj.202000826R
doi:
Substances chimiques
LINGO1 protein, mouse
0
Lingo2 protein, mouse
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13641-13653Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
Carim-Todd L, Escarceller M, Estivill X, Sumoy L. LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex. Eur J Neurosci. 2003;18:3167-3182.
Homma S, Shimada T, Hikake T, Yaginuma H. Expression pattern of LRR and Ig domain-containing protein (LRRIG protein) in the early mouse embryo. Gene Expr Patterns. 2009;9:1-26.
Chen Y, Aulia S, Li L, Tang BL. AMIGO and friends: an emerging family of brain-enriched, neuronal growth modulating, type I transmembrane proteins with leucine-rich repeats (LRR) and cell adhesion molecule motifs. Brain Res Rev. 2006;51:265-274.
Barrette B, Vallieres N, Dube M, Lacroix S. Expression profile of receptors for myelin-associated inhibitors of axonal regeneration in the intact and injured mouse central nervous system. Mol Cell Neurosci. 2007;34:519-538.
Llorens F, Gil V, Iraola S, et al. Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain: interaction of its intracellular domain with Myt1l. Dev Neurobiol. 2008;68:521-541.
Mi S, Lee X, Shao Z, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004;7:221-228.
Okafuji T, Tanaka H. Expression pattern of LINGO-1 in the developing nervous system of the chick embryo. Gene Expr Patterns. 2005;6:57-62.
Haines BP, Rigby PW. Expression of the Lingo/LERN gene family during mouse embryogenesis. Gene Expr Patterns. 2008;8:79-86.
Andrews JL, Fernandez-Enright F. A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders. Neurosci Biobehav Rev. 2015;56:97-114.
Llorens F, Gil V, del Rio JA. Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration. FASEB J. 2011;25:463-475.
Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic. CNS Drugs. 2013;27:493-503.
Petrillo J, Balcer L, Galetta S, Chai Y, Xu L, Cadavid D. Initial impairment and recovery of vision-related functioning in participants with acute optic neuritis from the RENEW trial of opicinumab. J Neuroophthalmol. 2019;39:153-160.
Aktas O, Albrecht P, Hartung HP. Optic neuritis as a phase 2 paradigm for neuroprotection therapies of multiple sclerosis: update on current trials and perspectives. Curr Opin Neurol. 2016;29:199-204.
Pepinsky RB, Arndt JW, Quan C, et al. Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy. J Pharmacol Exp Ther. 2014;350:110-123.
Shao Z, Lee X, Huang G, et al. LINGO-1 regulates oligodendrocyte differentiation through the cytoplasmic gelsolin signaling pathway. J Neurosci. 2017;37:3127-3137.
Cadavid D, Mellion M, Hupperts R, et al. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 18(9), 845-856.
Park JB, Yiu G, Kaneko S, et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron. 2005;45:345-351.
Shao Z, Browning JL, Lee X, et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron. 2005;45:353-359.
Yamashita T, Fujitani M, Yamagishi S, Hata K, Mimura F. Multiple signals regulate axon regeneration through the Nogo receptor complex. Mol Neurobiol. 2005;32:105-111.
Inoue H, Lin L, Lee X, et al. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Natl Acad Sci U S A. 2007;104:14430-14435.
Lee X, Shao Z, Sheng G, Pepinsky B, Mi S. LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts. Mol Cell Neurosci. 2014;60:36-42.
Mandai K, Guo T, St Hillaire C, et al. LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development. Neuron. 2009;63:614-627.
Meabon JS, de Laat R, Ieguchi K, et al. Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling. Mol Cell Neurosci. 2016;70:1-10.
Zhang Z, Xu X, Zhang Y, Zhou J, Yu Z, He C. LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension. J Biol Chem. 2009;284:15717-15728.
Zhang Z, Xu X, Xiang Z, Yu Z, Feng J, He C. LINGO-1 receptor promotes neuronal apoptosis by inhibiting WNK3 kinase activity. J Biol Chem. 2013;288:12152-12160.
Mosyak L, Wood A, Dwyer B, et al. The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition. J Biol Chem. 2006;281:36378-36390.
Cobret L, De Tauzia ML, Ferent J, et al. Targeting the cis-dimerization of LINGO-1 with low MW compounds affects its downstream signalling. Br J Pharmacol. 2015;172:841-856.
Traiffort E, Charytoniuk D, Watroba L, Faure H, Sales N, Ruat M. Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system. Eur J Neurosci. 1999;11:3199-3214.
Achour L, Kamal M, Jockers R, Marullo S. Using quantitative BRET to assess G protein-coupled receptor homo- and heterodimerization. Methods Mol Biol. 2011;756:183-200.
El Khamlichi C, Reverchon-Assadi F, Hervouet-Coste N, Blot L, Reiter E, Morisset-Lopez S. Bioluminescence resonance energy transfer as a method to study protein-protein interactions: application to G protein coupled receptor biology. Molecules. 2019;24:537.
James JR, Oliveira MI, Carmo AM, Iaboni A, Davis SJ. A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods. 2006;3:1001-1006.
Jepson S, Vought B, Gross CH, et al. LINGO-1, a transmembrane signaling protein, inhibits oligodendrocyte differentiation and myelination through intercellular self-interactions. J Biol Chem. 2012;287:22184-22195.
Stein T, Walmsley AR. The leucine-rich repeats of LINGO-1 are not required for self-interaction or interaction with the amyloid precursor protein. Neurosci Lett. 2012;509:9-12.
Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M. Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer. J Biol Chem. 2002;277:44925-44931.
Wang D, Sun X, Bohn LM, Sadee W. Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer. Mol Pharmacol. 2005;67:2173-2184.
Couturier C, Jockers R. Activation of the leptin receptor by a ligand-induced conformational change of constitutive receptor dimers. J Biol Chem. 2003;278:26604-26611.
Kobe B, Kajava AV. The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol. 2001;11:725-732.
Maness PF, Schachner M. Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat Neurosci. 2007;10:19-26.