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The Journal of Neuroscience, January 1, 2000, 20(1):427-437

The Glial Cell Line-Derived Neurotrophic Factor Family Receptor Components Are Differentially Regulated within Sensory Neurons after Nerve Injury

David L. H. Bennett¹, Timothy J. Boucher¹, Mark P. Armanini², Kris T. Poulsen², Gregory J. Michael³, John V. Priestley³, Heidi S. Phillips², Stephen B. McMahon¹, and David L. Shelton²

¹ Neuroscience Research Centre, St. Thomas' Hospital Campus, GKT, King's College London, London, SE1 7EH, United Kingdom, ² Department of Neuroscience, Genentech Inc., South San Francisco, California 94080, and ³ Neuroscience Section, Division of Biomedical Sciences, Queen Mary and Westfield College, London, E1 4NS, United Kingdom

Glial cell line-derived neurotrophic factor (GDNF) has potent trophic effects on adult sensory neurons after nerve injury and is one of a family of proteins that includes neurturin, persephin, and artemin. Sensitivity to these factors is conferred by a receptor complex consisting of a ligand binding domain (GFR1-GFR4) and a signal transducing domain RET. We have investigated the normal expression of GDNF family receptor components within sensory neurons and the response to nerve injury.

In normal rats, RET and GFR1 were expressed in a subpopulation of both small- and large-diameter afferents projecting through the sciatic nerve [60 and 40% of FluoroGold (FG)-labeled cells, respectively]. GFR2 and GFR3 were both expressed principally within small-diameter DRG cells (30 and 40% of FG-labeled cells, respectively). Two weeks after sciatic axotomy, the expression of GFR2 was markedly reduced (to 12% of sciatic afferents). In contrast, the proportion of sciatic afferents that expressed GFR1 increased (to 66% of sciatic afferents) so that virtually all large-diameter afferents expressed this receptor component, and the expression of GFR3 also increased (to 66% of sciatic afferents) so that almost all of the small-diameter afferents expressed this receptor component after axotomy. There was little change in RET expression.

The changes in the proportions of DRG cells expressing different receptor components were mirrored by alterations in the total RNA levels within the DRG. The changes in GFR1 and GFR2 expression after axotomy could be largely reversed by treatment with GDNF.

Key words: GDNF receptor expression; GFR; RET; axotomy; DRG; rat

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Copyright © 2000 Society for Neuroscience  0270-6474/0/201427-11$05.00/0

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