Soluble LILRA3 promotes neurite outgrowth and synapses formation through a high-affinity interaction with Nogo 66

Hongyan An, Merryn Brettle, Terry Lee, Benjamin Heng, Chai K. Lim, Gilles J. Guillemin, Megan S. Lord, Enrico Klotzsch, Carolyn L. Geczy, Katherine Bryant, Thomas Fath, Nicodemus Tedla*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1198-1209
Number of pages12
JournalJournal of Cell Science
Volume129
Issue number6
DOIs
Publication statusPublished - 2016

Keywords

  • Cortical neuron
  • Leukocyte immunoglobulin-like receptor A3
  • Neurite outgrowth
  • Nogo 66
  • PIRB
  • Synapse

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