Baloh R H, Tansey M G, Golden J P, Creedon D J, Heuckeroth R O, Keck C L, Zimonjic D B, Popescu N C, Johnson E M, Milbrandt J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Neuron. 1997 May;18(5):793-802. doi: 10.1016/s0896-6273(00)80318-9.
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a family of TGF-beta-related neurotrophic factors (TRNs), which have trophic influences on a variety of neuronal populations. A receptor complex comprised of TrnR1 (GDNFR alpha) and Ret was recently identified and found to be capable of mediating both GDNF and NTN signaling. We have identified a novel receptor based on homology to TrnR1, called TrnR2, that is 48% identical to TrnR1, and is located on the short arm of chromosome 8. TrnR2 is attached to the cell surface via a GPI-linkage, and can mediate both NTN and GDNF signaling through Ret in vitro. Fibroblasts expressing TrnR2 and Ret are approximately 30-fold more sensitive to NTN than to GDNF treatment, whereas those expressing TrnR1 and Ret respond equivalently to both factors, suggesting the TrnR2-Ret complex acts preferentially as a receptor for NTN. TrnR2 and Ret are expressed in neurons of the superior cervical and dorsal root ganglia, and in the adult brain. Comparative analysis of TrnR1, TrnR2, and Ret expression indicates that multiple receptor complexes, capable of mediating GDNF and NTN signaling, exist in vivo.
胶质细胞系源性神经营养因子（GDNF）和神经营养素（NTN）构成了一个与转化生长因子-β相关的神经营养因子（TRNs）家族，它们对多种神经元群体具有营养作用。最近鉴定出一种由TrnR1（GDNFRα）和Ret组成的受体复合物，发现其能够介导GDNF和NTN信号传导。我们基于与TrnR1的同源性鉴定出一种新型受体，称为TrnR2，它与TrnR1有48%的同一性，位于8号染色体短臂上。TrnR2通过糖基磷脂酰肌醇（GPI）连接附着于细胞表面，并且在体外能够通过Ret介导NTN和GDNF信号传导。表达TrnR2和Ret的成纤维细胞对NTN的敏感性比对GDNF处理高约30倍，而表达TrnR1和Ret的细胞对这两种因子的反应相当，这表明TrnR2-Ret复合物优先作为NTN的受体起作用。TrnR2和Ret在上颈神经节和背根神经节的神经元以及成体大脑中表达。对TrnR1、TrnR2和Ret表达的比较分析表明，体内存在多种能够介导GDNF和NTN信号传导的受体复合物。
