Tissue expression of alternatively spliced GFRalpha1, NCAM and RET isoforms and the distinct functional consequence of ligand-induced activation of GFRalpha1 isoforms.
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.
Department of Biochemistry, National University of Singapore, Lower Kent Ridge Road, Singapore 119260, Singapore.
Li Foong
LF
Yoong
Zhong Ni
ZN
Peng
Guoqiang
G
Wan
Heng-Phon
HP
Too
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
C494988:Gfra1 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases