Alternative splicing affecting a novel domain in the C-elegans EGL-15 FGF receptor confers functional specificity
Alternative splicing affecting a novel domain in the C-elegans EGL-15 FGF receptor confers functional specificity
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DOI：
10.1242/dev.00604
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发表时间：
2003-08-01
期刊：
影响因子：
4.6
通讯作者：
Stern, MJ
中科院分区：
文献类型：
--
作者：
Goodman, SJ;Branda, CS;Stern, MJ
成纤维细胞生长因子 (FGF) 受体触发多种细胞反应，包括细胞迁移、细胞增殖和细胞分化。然而，这些反应特异性的分子基础尚不清楚。线虫 FGF 受体 EGL-15 类似地介导许多不同的反应，包括转导化学吸引信号和介导基本功能。对egl-15 迁移特异性等位基因的分析发现了一种新的EGL-15 亚型，该亚型为该位点病变的不同表型效应提供了分子解释。选择性剪接产生两种 EGL-15 蛋白，其中含有不同形式的结构域，位于紧邻第一个 IG 结构域之后的受体胞外区域内。这两种结构域形式均未在任何其他 FGF 受体中发现。我们测试了这些 EGL-15 受体亚型及其两种 FGF 配体的信号传导特异性。我们的分析证明了两种受体变体的不同生理功能。 EGL-15(5A) 是对 FGF 趋化剂作出反应所必需的，引导性成肌细胞迁移至最终位置。相比之下，EGL-15(5B) 对于引发该受体介导的基本功能来说既是必要的又是充分的。
Fibroblast growth factor (FGF) receptors trigger a wide variety of cellular responses as diverse as cell migration, cell proliferation and cell differentiation. However, the molecular basis of the specificity of these responses is not well understood. The C elegans FGF receptor EGL-15 similarly mediates a number of different responses, including transducing a chemoattractive signal and mediating an essential function. Analysis of the migration-specific alleles of egl-15 has identified a novel EGL-15 isoform that provides a molecular explanation for the different phenotypic effects of lesions at this locus. Alternative splicing yields two EGL-15 proteins containing different forms of a domain located within the extracellular region of the receptors immediately after the first IG domain. Neither of these two domain forms is found in any other FGF receptor. We have tested the roles of these EGL-15 receptor isoforms and their two FGF ligands for their signaling specificity. Our analyses demonstrate different physiological functions for the two receptor variants. EGL-15(5A) is required for the response to the FGF chemoattractant that guides the migrating sex myoblasts to their final positions. By contrast, EGL-15(5B) is both necessary and sufficient to elicit the essential function mediated by this receptor.