GFRalpha3 is expressed predominantly in nociceptive sensory neurons


: Dr Michele Sanicola, as above.


Activation of the RET receptor tyrosine kinase by glial-derived neurotrophic factor family members is dependent on a family of coreceptors, GFRα1–4. GFRα3 preferentially binds the newest member of the glial-derived neurotrophic factor family of ligands, artemin. The major site of GFRα3 expression is in the dorsal root ganglion; however, the class of sensory neurons that expresses GFRα3 has not been reported previously. Using immunohistochemical methods, we show that the majority of dorsal root ganglion cells that express GFRα3 also express vanilloid receptor type 1, peripherin, RET, trkA and calcitonin gene-related peptide. In addition, a significant subpopulation of GFRα3-expressing cells also binds the lectin IB4. We demonstrate that GFRα3 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.