Soluble LILRA3 promotes neurite outgrowth and synapses formation through a high-affinity interaction with Nogo 66
| Autor: | Benjamin Heng, Enrico Klotzsch, Terry Lee, Chai K. Lim, Hongyan An, Megan S. Lord, Thomas Fath, Merryn Brettle, Carolyn L. Geczy, Nicodemus Tedla, Gilles J. Guillemin, Katherine Bryant |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Neurite Neurogenesis Nogo Proteins Neuronal Outgrowth Biology Inhibitory postsynaptic potential Bioinformatics Synapse 03 medical and health sciences Mice LILRB2 mental disorders Neurites Animals Humans Receptors Immunologic Receptor Cells Cultured Neurons Cell Biology Cell biology Mice Inbred C57BL 030104 developmental biology Competitive antagonist Synapses LILRA3 psychological phenomena and processes Protein Binding |
| Zdroj: | Journal of cell science. 129(6) |
| ISSN: | 1477-9137 |
| Popis: | Inhibitory proteins, particularly Nogo 66, a highly conserved 66-amino-acid loop of Nogo A (an isoform of RTN4), play key roles in limiting the intrinsic capacity of the central nervous system (CNS) to regenerate after injury. Ligation of surface Nogo receptors (NgRs) and/or leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue the paired immunoglobulin-like receptor B (PIRB) by Nogo 66 transduces inhibitory signals that potently inhibit neurite outgrowth. Here, we show that soluble leukocyte immunoglobulin-like receptor A3 (LILRA3) is a high-affinity receptor for Nogo 66, suggesting that LILRA3 might be a competitive antagonist to these cell surface inhibitory receptors. Consistent with this, LILRA3 significantly reversed Nogo-66-mediated inhibition of neurite outgrowth and promoted synapse formation in primary cortical neurons through regulation of the ERK/MEK pathway. LILRA3 represents a new antagonist to Nogo-66-mediated inhibition of neurite outgrowth in the CNS, a function distinct from its immune-regulatory role in leukocytes. This report is also the first to demonstrate that a member of LILR family normally not expressed in rodents exerts functions on mouse neurons through the highly homologous Nogo 66 ligand. |
| Databáze: | OpenAIRE |
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