期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：3
页码：1295-1300
DOI：10.1073/pnas.95.3.1295
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We report the identification of an additional member of the glial cell line-derived neurotrophic factor (GDNF) family receptor, termed GFR3, that is homologous to the previously identified GDNF and neurturin ligand binding receptors GFR1 and GFR2. GFR3 is 32% and 37% identical to GFR1 and GFR2, respectively. RNase protection assays show that whereas gfr1 and gfr2 are abundant in both developing and adult brain, gfr3 is exclusively expressed during development. All receptors are widely present in both the developing and adult peripheral nervous system and in peripheral organs. For instance, in situ hybridization shows that the developing liver, stomach, intestine, kidney, and sympathetic chain, which all contain ret-expressing cells, transcribe unique complementary and overlapping patterns of most or all of the GDNF family receptors and ligands. In sensory neurons of the trigeminal ganglion gfr2 and gfr3 are expressed in different subpopulations of neurons, whereas gfr1 is coexpressed in some gfr2 and gfr3-positive neurons. We find that the gfr1 population of trigeminal neurons is absent in GDNF null mutant mice, suggesting that GDNF signals in vivo by interacting with GFR1. Thus, our results show that there are at least three members in the GDNF family of ligand binding receptors and that these receptors may be crucial in conferring ligand specificity in vivo. The unique complementary and overlapping expression of gfr3 implies distinct functions in the developing and adult mouse from that of GFR1 and GFR2.
