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The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho

Toshihide Yamashita1, Haruhisa Higuchi, Masaya Tohyama

  • 1Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. tyama@anat2.med.osaka-u.ac.jp

The Journal of Cell Biology
|May 16, 2002
PubMed

Insights

The neurotrophin receptor p75 (p75(NTR)) acts as the receptor for myelin-associated glycoprotein (MAG), inhibiting neurite outgrowth. This discovery identifies a key pathway for neuronal development and regeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Myelin-associated glycoprotein (MAG) inhibits neuronal outgrowth.
  • The specific receptor and signaling pathway for MAG have not been identified.

Purpose of the Study:

  • To identify the signal-transducing receptor for MAG.
  • To elucidate the molecular mechanism by which MAG inhibits neurite outgrowth.

Main Methods:

  • Utilized genetically modified mice lacking functional p75(NTR).
  • Assessed neurite outgrowth in response to MAG in different neuronal populations.
  • Investigated the activation of small GTPase RhoA.
  • Examined the colocalization of p75(NTR) and MAG binding.
  • Analyzed the association of ganglioside GT1b with p75(NTR).

Main Results:

  • Neurons from p75(NTR) mutant mice were insensitive to MAG's inhibitory effects on neurite outgrowth.
  • MAG activates RhoA signaling, leading to inhibited outgrowth in the presence of p75(NTR).
  • p75(NTR) and MAG binding sites colocalized on neurons.
  • Ganglioside GT1b, a MAG binding partner, specifically associated with p75(NTR).

Conclusions:

  • The neurotrophin receptor p75(NTR) functions as the signal-transducing receptor for MAG.
  • A complex of p75(NTR) and ganglioside GT1b likely mediates MAG's inhibitory signals in neurons.
  • This finding has implications for understanding neuronal development and potential therapeutic strategies for nerve repair.

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