Baloh R H, Gorodinsky A, Golden J P, Tansey M G, Keck C L, Popescu N C, Johnson E M, Milbrandt J
Department of Pathology and Internal Medicine, Molecular Biology, and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1998 May 12;95(10):5801-6. doi: 10.1073/pnas.95.10.5801.
GDNF, neurturin, and persephin are transforming growth factor beta-related neurotrophic factors known collectively as the GDNF family (GF). GDNF and neurturin signal through a multicomponent receptor complex containing a signaling component (the Ret receptor tyrosine kinase) and either of two glycosyl-phosphatidylinositol-linked binding components (GDNF family receptor alpha components 1 and 2, GFRalpha1 or GFRalpha2), whereas the receptor for persephin is unknown. Herein we describe a third member of the GF coreceptor family called GFRalpha3 that is encoded by a gene located on human chromosome 5q31.2-32. GFRalpha3 is not expressed in the central nervous system of the developing or adult animal but is highly expressed in several developing and adult sensory and sympathetic ganglia of the peripheral nervous system. GFRalpha3 is also expressed at high levels in developing, but not adult, peripheral nerve. GFRalpha3 is a glycoprotein that is glycosyl-phosphatidylinositol-linked to the cell surface like GFRalpha1 and GFRalpha2. Fibroblasts expressing Ret and GFRalpha3 do not respond to any of the known members of the GDNF family, suggesting that GFRalpha3 interacts with an unknown ligand or requires a different or additional signaling protein to function.
胶质细胞源性神经营养因子（GDNF）、神经营养素和persephin是转化生长因子β相关的神经营养因子，统称为GDNF家族（GF）。GDNF和神经营养素通过一种多组分受体复合物发出信号，该复合物包含一个信号组分（Ret受体酪氨酸激酶）和两种糖基磷脂酰肌醇连接的结合组分之一（GDNF家族受体α组分1和2，GFRα1或GFRα2），而persephin的受体尚不清楚。在此，我们描述了GF共受体家族的第三个成员，称为GFRα3，它由位于人类染色体5q31.2 - 32上的一个基因编码。GFRα3在发育中的或成年动物的中枢神经系统中不表达，但在周围神经系统的几个发育中的和成年的感觉和交感神经节中高度表达。GFRα3在发育中的外周神经中也高水平表达，但在成年外周神经中不表达。GFRα3是一种糖蛋白，与GFRα1和GFRα2一样，通过糖基磷脂酰肌醇连接到细胞表面。表达Ret和GFRα3的成纤维细胞对GDNF家族的任何已知成员均无反应，这表明GFRα3与一种未知配体相互作用，或者需要一种不同的或额外的信号蛋白来发挥作用。
