Tissue expression of alternatively spliced GFRα1, NCAM and RET isoforms and the distinct functional consequence of ligand-induced activation of GFRα1 isoforms

Glial-cell-line-derived neurotrophic factor (GDNF) exerts its effect through a multi-component receptor system consisting of GFRα1, RET and NCAM. Two highly homologous alternatively spliced GFRα1 isoforms (GFRα1a and GFRα1b) have previously been identified. In this study, isoform specific real-time PCR assays were used to quantify the expression levels of GFRα1, RET and NCAM isoforms in murine embryonic and adult tissues. The expression levels of GFRα1b were found to be comparable to that of GFRα1a in peripheral tissues. However, GFRα1a was the predominant isoform expressed in the whole brain. The co-expressions of GFRα1 and the co-receptors were developmentally regulated and differentially expressed in some tissues. Microarray analyses of GFRα1 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 GFRα, RET and NCAM may contribute to the pleiotropic biological responses.