Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth

J Biol Chem. 2012 Oct 26;287(44):37171-84. doi: 10.1074/jbc.M112.389916. Epub 2012 Aug 24.

Abstract

Olfm1, a secreted highly conserved glycoprotein, is detected in peripheral and central nervous tissues and participates in neural progenitor maintenance, cell death in brain, and optic nerve arborization. In this study, we identified Olfm1 as a molecule promoting axon growth through interaction with the Nogo A receptor (NgR1) complex. Olfm1 is coexpressed with NgR1 in dorsal root ganglia and retinal ganglion cells in embryonic and postnatal mice. Olfm1 specifically binds to NgR1, as judged by alkaline phosphatase assay and coimmunoprecipitation. The addition of Olfm1 inhibited the growth cone collapse of dorsal root ganglia neurons induced by myelin-associated inhibitors, indicating that Olfm1 attenuates the NgR1 receptor functions. Olfm1 caused the inhibition of NgR1 signaling by interfering with interaction between NgR1 and its coreceptors p75NTR or LINGO-1. In zebrafish, inhibition of optic nerve extension by olfm1 morpholino oligonucleotides was partially rescued by dominant negative ngr1 or lingo-1. These data introduce Olfm1 as a novel NgR1 ligand that may modulate the functions of the NgR1 complex in axonal growth.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Axons / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • COS Cells
  • Chlorocebus aethiops
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix Proteins / physiology*
  • Glycoproteins / metabolism
  • Glycoproteins / physiology*
  • Green Fluorescent Proteins / biosynthesis
  • Growth Cones / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Proteins / physiology
  • Nerve Tissue Proteins / metabolism*
  • Nogo Proteins
  • Optic Nerve / cytology
  • Optic Nerve / embryology
  • Organ Specificity
  • PC12 Cells
  • Protein Binding
  • Rats
  • Receptor, Nerve Growth Factor / metabolism
  • Zebrafish
  • Zebrafish Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Extracellular Matrix Proteins
  • Glycoproteins
  • LINGO1 protein, human
  • Membrane Proteins
  • Myelin Proteins
  • Nerve Tissue Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Receptor, Nerve Growth Factor
  • Rtn4 protein, mouse
  • Rtn4 protein, rat
  • Rtn4a protein, zebrafish
  • Zebrafish Proteins
  • enhanced green fluorescent protein
  • neurog1 protein, zebrafish
  • olfactomedin
  • Green Fluorescent Proteins
  • rhoA GTP-Binding Protein