Identification and characterization of GFRα-3, a novel co-receptor belonging to the glial cell line-derived neurotrophic receptor family
Identification and characterization of GFRα-3, a novel co-receptor belonging to the glial cell line-derived neurotrophic receptor family
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DOI：
10.1074/jbc.273.6.3502
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发表时间：
1998-02-06
影响因子：
4.8
通讯作者：
Dixon, JE
中科院分区：
文献类型：
--
作者：
Worby, CA;Vega, QC;Dixon, JE
最近已经描述了一个新的神经元存活因子家族，其包括胶质细胞系衍生的神经营养因子（GDNF）和neurturin（Kotzbauer，P.T.，兰普，宾夕法尼亚州，赫克罗斯河，巴西-地O.，戈尔登，J. P.，Creedon，D. J.，约翰逊，E. M.，小的，和Milbrandt，J.（1997）Nature 384，467-470），这些与转化生长因子-β相关的分子在胚胎发生和不同神经元群体的存活中是重要的。这些分子通过包括Ret受体酪氨酸激酶（一种配体）的新受体系统发出信号（即GDNF或neurturin），和负责配体的高亲和力结合的辅助糖基-磷脂酰肌醇连接分子，两个辅助分子表示GDNF家族受体1和2（GFR α-1和GFR α-2）在GDNF和neurturin信号传导复合物中起作用，基于与GFR α-1的相似性，我们已经确定了一种属于该家族的新型辅助受体，我们将其命名为GFR α-3。GFR α-3与GFR α-1显示33%的氨基酸同一性，与GFR α-2显示36%的同一性。尽管GFR α-3与GFR α-1和GFR α-2相似，但它不能与GDNF一起激活Ret，这表明可能还有其他未发现的配体和/或待鉴定的Ret样受体。GFR α-3通过磷脂酰肌醇特异性磷脂酶C抗性糖基-磷脂酰肌醇键锚定在细胞膜上，GFR α-3在胚胎11天高度表达，但在成年小鼠中不明显表达。原位杂交分析表明GFR α-3位于背根神经节和上级颈交感神经节。GFR alpha-3和Ret表达模式的比较表明，这些分子可以形成一个受体对，并与GDNF家族成员相互作用，在发育中发挥独特的作用。
A new family of neuronal survival factors comprised of glial cell line-derived neurotrophic factor (GDNF) and neurturin has recently been described (Kotzbauer, P. T., Lampe, P. A., Heuckeroth, R. O., Golden, J. P., Creedon, D. J., Johnson, E. M., Jr., and Milbrandt, J. (1997) Nature 384, 467-470), These molecules, which are related to transforming growth factor-beta, are important in embryogenesis and in the survival of distinct neuronal populations, These molecules signal through a novel receptor system that includes the Ret receptor tyrosine kinase, a ligand (i.e. GDNF or neurturin), and an accessory glycosyl-phosphatidylinositol-linked molecule that is responsible for high affinity binding of the ligand, Two accessory molecules denoted GDNF family receptor 1 and 2 (GFR alpha-1 and GFR alpha-2) have been described that function in GDNF and neurturin signaling complexes, We have identified a novel co-receptor belonging to this family based on similarity to GFR alpha-1, which we have named GFR alpha-3. GFR alpha-3 displays 33% amino acid identity with GFR alpha-1 and 36% identity with GFR alpha-2. Despite the similarity of GFR alpha-3 to GFR alpha-1 and GFR alpha-2, it is unable to activate Ret in conjunction with GDNF, suggesting that there are likely additional undiscovered ligands and/or Ret-like receptors to be identified, GFR alpha-3 is anchored to the cell membrane by a phosphatidylinositol-specific phospholipase C-resistant glycosyl-phosphatidylinositol linkage, GFR alpha-3 is highly expressed by embryonic day 11 but is not appreciably expressed in the adult mouse, In situ hybridization analyses demonstrate that GFR alpha-3 is located in dorsal root ganglia and the superior cervical sympathetic ganglion. Comparison of the expression patterns of GFR alpha-3 and Ret suggests that these molecules could form a receptor pair and interact with GDNF family members to play unique roles in development.