Yoong Li Foong, Peng Zhong Ni, Wan Guoqiang, Too Heng-Phon
Department of Biochemistry, National University of Singapore, Lower Kent Ridge Road, Singapore 119260, Singapore.
Brain Res Mol Brain Res. 2005 Sep 13;139(1):1-12. doi: 10.1016/j.molbrainres.2005.05.016.
Glial-cell-line-derived neurotrophic factor (GDNF) exerts its effect through a multi-component receptor system consisting of GFRalpha1, RET and NCAM. Two highly homologous alternatively spliced GFRalpha1 isoforms (GFRalpha1a and GFRalpha1b) have previously been identified. In this study, isoform specific real-time PCR assays were used to quantify the expression levels of GFRalpha1, RET and NCAM isoforms in murine embryonic and adult tissues. The expression levels of GFRalpha1b were found to be comparable to that of GFRalpha1a in peripheral tissues. However, GFRalpha1a was the predominant isoform expressed in the whole brain. The co-expressions of GFRalpha1 and the co-receptors were developmentally regulated and differentially expressed in some tissues. Microarray analyses of GFRalpha1 isoforms transfected cells stimulated with NTN showed distinct and non-overlapping gene profiles. These observations are consistent with the emerging view that the combinatorial interactions of the spliced isoforms of GFRalpha, RET and NCAM may contribute to the pleiotropic biological responses.
胶质细胞系源性神经营养因子（GDNF）通过由GFRα1、RET和NCAM组成的多组分受体系统发挥作用。此前已鉴定出两种高度同源的选择性剪接GFRα1异构体（GFRα1a和GFRα1b）。在本研究中，使用异构体特异性实时PCR测定法来定量小鼠胚胎和成年组织中GFRα1、RET和NCAM异构体的表达水平。发现GFRα1b在外周组织中的表达水平与GFRα1a相当。然而，GFRα1a是全脑中表达的主要异构体。GFRα1与共受体的共表达受发育调控，且在某些组织中差异表达。用NTN刺激的转染GFRα1异构体的细胞的微阵列分析显示出不同且不重叠的基因谱。这些观察结果与新出现的观点一致，即GFRα、RET和NCAM剪接异构体的组合相互作用可能导致多效性生物学反应。
