The neurotransmitter glutamate reduces axonal responsiveness to multiple repellents through the activation of metabotropic glutamate receptor 1

J Neurosci. 2004 Aug 11;24(32):7085-95. doi: 10.1523/JNEUROSCI.0349-04.2004.

Abstract

Glutamate is the major excitatory neurotransmitter in the mammalian CNS. Here, we propose a new role for this neurotransmitter in the developing nervous system. We show that glutamate or the metabotropic class I agonist S-3,5-dihydroxyphenyl glycine, acting through the metabotropic glutamate receptor 1 (mGluR1), can reduce the activity of multiple axonal repellents in vitro. This effect is mediated by a pertussis toxin-sensitive activation of protein kinase A and the subsequent inactivation of Rho. This signaling pathway appears to be identical to the one we described previously for stromal derived factor-1-induced reduction of axonal repellent activities. Activation of mGluR1 can also promote increased survival of embryonic retinal ganglion cells in culture. We propose that neurotransmitter-induced modulation of repellent strength provides a novel mechanism by which activity can influence neuronal morphology.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Cell Survival
  • Cells, Cultured
  • Chick Embryo
  • Cyclic AMP / physiology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Embryo, Mammalian / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism
  • Glutamic Acid / pharmacology
  • Glutamic Acid / physiology*
  • Growth Cones / drug effects
  • Growth Cones / physiology
  • Intercellular Signaling Peptides and Proteins
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Nerve Tissue Proteins / physiology*
  • Protein Transport
  • Receptors, CXCR4 / agonists
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / biosynthesis
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Semaphorin-3A / physiology
  • Semaphorins / physiology*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Receptors, CXCR4
  • Receptors, Metabotropic Glutamate
  • Semaphorin-3A
  • Semaphorins
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • Methoxyhydroxyphenylglycol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • rho GTP-Binding Proteins
  • Slit homolog 2 protein
  • 3,4-dihydroxyphenylglycol