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PirB is a functional receptor for myelin inhibitors of axonal regeneration

Jasvinder K Atwal1, Julie Pinkston-Gosse, Josh Syken

  • 1Neurodegeneration Labs and Research Drug Discovery, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

Science (New York, N.Y.)
|November 8, 2008
PubMed

Insights

Paired immunoglobulin-like receptor B (PirB) is a novel receptor for myelin-associated inhibitors of axon regeneration. Blocking PirB and Nogo receptor (NgR) activity together promotes significant axon regrowth after injury.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Mammalian central nervous system axon regeneration is hindered by inhibitory myelin proteins like Nogo, MAG, and OMgp.
  • These proteins bind to the Nogo receptor (NgR), but NgR deletion alone yields limited regeneration, suggesting other receptors exist.

Purpose of the Study:

  • To identify additional receptors for myelin-associated axon growth inhibitors.
  • To investigate the role of paired immunoglobulin-like receptor B (PirB) in mediating regeneration blockade.

Main Methods:

  • Expression cloning was used to identify PirB as a high-affinity receptor for Nogo, MAG, and OMgp.
  • Neurite inhibition assays were performed using antibodies and genetic manipulation of PirB and NgR.

Main Results:

  • PirB binds Nogo, MAG, and OMgp with high affinity.
  • Interference with PirB partially rescued neurite outgrowth inhibition by myelin components.
  • Combined blockade of PirB and NgR nearly abolished myelin-induced inhibition.

Conclusions:

  • PirB mediates myelin-associated inhibition of central nervous system axon regeneration.
  • PirB represents a potential therapeutic target for promoting axon repair.
  • This finding explains enhanced visual plasticity in PirB and NgR knockout mice.

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