Evolution of the GDNF family ligands and receptors
Evolution of the GDNF family ligands and receptors
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DOI：
10.1159/000094087
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发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Hatinen, Tuomas
中科院分区：
文献类型：
--
作者：
Airaksinen, Matti S.;Holm, Liisa;Hatinen, Tuomas
GDNF（胶质细胞源性神经营养因子）家族中存在四种不同的配体-受体结合对，它们都通过跨膜RET受体酪氨酸激酶进行信号传导。此外，功能未知的GRAL（GDNF受体α样）蛋白和Gas 1（生长停滞特异性1）具有GDNF家族受体（GFR）样结构域。四种GFR α受体GRAL和Gas 1的直系同源物存在于所有脊椎动物类别中。相反，尽管硬骨鱼具有所有四种GDNF家族配体（GFL）的直系同源物，但其中一种配体neurturin在爪蛙中不存在，另一种配体persephin在鸡基因组中不存在。青蛙GFR α 2有选择性地进化，可能是为了适应GDNF作为配体。GDNF及其受体GFR α 1在肠神经系统发育中的关键作用从斑马鱼到人类都是保守的。neurturin的作用，通过GFR α 2的信号，副交感神经元的发展是保守的鸡和小鼠之间。artemin和persephin分别通过GFR α 3和GFR α 4发出信号，其作用在非哺乳动物中是未知的。RET和GFR样基因在昆虫中的存在表明，ProtoGFR和Proto-RET在两侧对称动物的进化早期就出现了，但是ProtoGFL何时与现有的转化生长因子（TGF β）样蛋白分离尚不清楚。四种GFLs和GFR α可能是由脊椎动物起源时的基因组复制产生的。青蛙neurturin和鸡persephin的缺失表明早期四足动物的功能冗余。非哺乳动物GFLs和前脊索动物RET和GFR样蛋白的功能仍有待探索。版权所有（c）2006 S. Karger AG，巴塞尔。
Four different ligand-receptor binding pairs of the GDNF (glial cell line-derived neurotrophic factor) family exist in mammals, and they all signal via the transmembrane RET receptor tyrosine kinase. In addition, GRAL (GDNF Receptor Alpha-Like) protein of unknown function and Gas1 (growth arrest specific 1) have GDNF family receptor (GFR)-like domains. Orthologs of the four GFR alpha receptors, GRAL and Gas1 are present in all vertebrate classes. in contrast, although bony fishes have orthologs of all four GDNF family ligands (GFLs), one of the ligands, neurturin, is absent in clawed frog and another, persephin, is absent in the chicken genome. Frog GFR alpha 2 has selectively evolved possibly to accommodate GDNF as a ligand. The key role of GDNF and its receptor GFR alpha 1 in enteric nervous system development is conserved from zebrafish to humans. The role of neurturin, signaling via GFR alpha 2, for parasympathetic neuron development is conserved between chicken and mice. The role of artemin and persephin that signal via GFR alpha 3 and GFR alpha 4, respectively, is unknown in non-mammals. The presence of RET- and GFR-like genes in insects suggests that a ProtoGFR and a Proto-RET arose early in the evolution of bilaterian animals, but when the ProtoGFL diverged from existing transforming growth factor (TGF beta)-like proteins remains unclear. The four GFLs and GFR alpha s were presumably generated by genome duplications at the origin of vertebrates. Loss of neurturin in frog and persephin in chicken suggests functional redundancy in early tetrapods. Functions of non-mammalian GFLs and prechordate RET and GFR-like proteins remain to be explored. Copyright (c) 2006 S. Karger AG, Basel.