The glial cell line-derived neurotrophic factor family receptor components are differentially regulated within sensory neurons after nerve injury
The glial cell line-derived neurotrophic factor family receptor components are differentially regulated within sensory neurons after nerve injury
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DOI：
10.1523/jneurosci.20-01-00427.2000
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发表时间：
2000-01-01
影响因子：
5.3
通讯作者：
Shelton, DL
中科院分区：
文献类型：
--
作者：
Bennett, DLH;Boucher, TJ;Shelton, DL
胶质细胞源性神经营养因子（GDNF）对神经损伤后的成年感觉神经元具有强有力的营养作用，并且是包括neurturin、persephin和artemin的蛋白质家族之一。对这些因子的敏感性由受体复合物赋予，该受体复合物由配体结合结构域（GFR α 1-GFR α 4）和信号转导结构域RET组成。我们研究了GDNF家族受体成分在感觉神经元内的正常表达和对神经损伤的反应。在正常大鼠中，RET和GFR α 1在通过坐骨神经投射的小直径和大直径传入神经的亚群中表达[分别为60%和40%的FluoroGold（FG）标记细胞]。GFR α 2和GFR α 3均主要在小直径DRG细胞内表达（分别占FG标记细胞的30%和40%）。坐骨神经切断后2周，GFR α 2的表达明显减少（至坐骨神经传入的12%）。相比之下，表达GFR α 1的坐骨神经传入的比例增加（至坐骨神经传入的66%），因此几乎所有大直径传入都表达该受体成分，GFR α 3的表达也增加（至坐骨神经传入的66%），因此几乎所有小直径传入都在轴突切断后表达该受体成分。RET表达变化不大，表达不同受体成分的DRG细胞比例的变化反映在DRG内总RNA水平的变化上。GDNF治疗可逆转轴突切断后GFR α 1和GFR α 2表达的变化。
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 (GFR alpha 1-GFR alpha 4) 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 GFR alpha 1 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]. GFR alpha 2 and GFR alpha 3 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 GFR alpha 2 was markedly reduced (to 12% of sciatic afferents). In contrast, the proportion of sciatic afferents that expressed GFR alpha 1 increased (to 66% of sciatic afferents) so that virtually all large-diameter afferents expressed this receptor component, and the expression of GFR alpha 3 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 GFR alpha 1 and GFR alpha 2 expression after axotomy could be largely reversed by treatment with GDNF.