Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth

Neuron. 1999 Nov;24(3):585-93. doi: 10.1016/s0896-6273(00)81114-9.


While the neurotrophin receptor p75NTR is expressed by many developing neurons, its function in cells escaping elimination by programmed cell death remains unclear. The lack of intrinsic enzymatic activity of p75NTR prompted a search for protein interactors expressed in the developing retina, which resulted in the identification of the GTPase RhoA. In transfected cells, p75NTR activated RhoA, and neurotrophin binding abolished RhoA activation. In cultured neurons, inactivation of Rho proteins mimicked the effect of neurotrophins by increasing the rate of neurite elongation. In vivo, axonal outgrowth was retarded in mice carrying a mutation in the p75NTR gene. These results indicate that p75NTR modulates in a ligand-dependent fashion the activity of intracellular proteins known to regulate actin assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Chick Embryo / cytology
  • Chick Embryo / physiology
  • Guanosine Diphosphate / metabolism
  • Ligands
  • Mice / embryology
  • Nerve Growth Factor / pharmacology
  • Nerve Growth Factors / metabolism*
  • Neurites / physiology
  • Neurons / physiology
  • Neurons, Afferent / physiology
  • Receptor, Nerve Growth Factor / metabolism*
  • Receptor, Nerve Growth Factor / physiology
  • Spinal Cord / embryology
  • rhoA GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / physiology


  • Ligands
  • Nerve Growth Factors
  • Receptor, Nerve Growth Factor
  • Guanosine Diphosphate
  • Nerve Growth Factor
  • rhoA GTP-Binding Protein