Abstract
Activation of the RET receptor tyrosine kinase by glial-derived neurotrophic factor family members is dependent on a family of coreceptors, GFRalpha1-4. GFRalpha3 preferentially binds the newest member of the glial-derived neurotrophic factor family of ligands, artemin. The major site of GFRalpha3 expression is in the dorsal root ganglion; however, the class of sensory neurons that expresses GFRalpha3 has not been reported previously. Using immunohistochemical methods, we show that the majority of dorsal root ganglion cells that express GFRalpha3 also express vanilloid receptor type 1, peripherin, RET, trkA and calcitonin gene-related peptide. In addition, a significant subpopulation of GFRalpha3-expressing cells also binds the lectin IB4. We demonstrate that GFRalpha3 artemin neurons are immunopositive for markers expected of nociceptors and include a subset of neurons distinct from the GDNF-responsive population. Our results indicate artemin may exert selective effects on pain sensation.
MeSH terms
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Animals
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Biomarkers
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Calcitonin Gene-Related Peptide / metabolism
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Drosophila Proteins*
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Female
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Ganglia, Spinal / cytology
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Ganglia, Spinal / metabolism*
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Immunohistochemistry
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Intermediate Filament Proteins / metabolism
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Lectins / metabolism
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Male
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Membrane Glycoproteins*
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Mice
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Mice, Inbred C57BL
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Nerve Tissue Proteins / metabolism
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Neurofilament Proteins / metabolism
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Neurons, Afferent / cytology
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Neurons, Afferent / metabolism*
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Nociceptors / cytology
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Nociceptors / metabolism*
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Pain / metabolism*
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Pain / physiopathology
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Peripherins
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-ret
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Rats
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Rats, Sprague-Dawley
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, trkA / metabolism
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Receptors, Cell Surface / metabolism*
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Receptors, Drug / metabolism
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Receptors, Nerve Growth Factor*
Substances
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Artn protein, mouse
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Artn protein, rat
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Biomarkers
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Drosophila Proteins
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Gfra1 protein, mouse
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Gfra3 protein, mouse
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Gfra3 protein, rat
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Intermediate Filament Proteins
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Lectins
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Neurofilament Proteins
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Peripherins
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, Drug
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Receptors, Nerve Growth Factor
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neurofilament protein H
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Receptor, trkA
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Ret protein, Drosophila
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Ret protein, mouse
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Ret protein, rat
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Calcitonin Gene-Related Peptide