The glial cell line-derived neurotrophic factor family receptor componentsare differentially regulated within sensory neurons after nerve injury

Glial cell line-derived neurotrophic factor (GDNF) has potent trophic effec ts on adult sensory neurons after nerve injury and is one of a family of pr oteins that includes neurturin, persephin, and artemin. Sensitivity to thes e factors is conferred by a receptor complex consisting of a ligand binding domain (GFR alpha 1-GFR alpha 4) and a signal transducing domain RET. We h ave investigated the normal expression of GDNF family receptor components w ithin sensory neurons and the response to nerve injury. In normal rats, RET and GFR alpha 1 were expressed in a subpopulation of bo th small- and large-diameter afferents projecting through the sciatic nerve [60 and 40% of FluoroGold (FG)-labeled cells, respectively]. GFR alpha 2 a nd GFR alpha 3 were both expressed principally within small-diameter DRG ce lls (30 and 40% of FG-labeled cells, respectively). Two weeks after sciatic axotomy, the expression of GFR alpha 2 was markedly reduced (to 12% of sci atic afferents). In contrast, the proportion of sciatic afferents that expr essed GFR alpha 1 increased (to 66% of sciatic afferents) so that virtually all large-diameter afferents expressed this receptor component, and the ex pression of GFR alpha 3 also increased (to 66% of sciatic afferents) so tha t almost all of the small-diameter afferents expressed this receptor compon ent after axotomy. There was little change in RET expression. The changes in the proportions of DRG cells expressing different receptor c omponents were mirrored by alterations in the total RNA levels within the D RG. The changes in GFR alpha 1 and GFR alpha 2 expression after axotomy cou ld be largely reversed by treatment with GDNF.