The neurotransmitter glutamate reduces axonal responsiveness to multiple repellents through the activation of metabotropic glutamate receptor 1.
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.
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Thomas A
TA
Kreibich
Sreekanth H
SH
Chalasani
Jonathan A
JA
Raper
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D021381:Protein Transport; D019718:Receptors, CXCR4 / Q000819:agonists; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000096:biosynthesis; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D040121:Semaphorin-3A / Q000502:physiology; D039961:Semaphorins / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000098552:Slit Homolog 2 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D019718:Receptors, CXCR4; D018094:Receptors, Metabotropic Glutamate; D040121:Semaphorin-3A; D039961:Semaphorins; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020741:rho GTP-Binding Proteins; D000098552:Slit Homolog 2 Protein; C010117:3,4-dihydroxyphenylglycol