Cell fate‐specific regulation of EGF receptor trafficking during Caenorhabditis elegans vulval development
Cell fate‐specific regulation of EGF receptor trafficking during Caenorhabditis elegans vulval development
复制标题
秀丽隐杆线虫外阴发育过程中 EGF 受体运输的细胞命运特异性调节
作者：
A. Stetak;Erika Fröhli Hoier;A. Croce;G. Cassata;P. P. Di Fiore;A. Hajnal
通过控制生长因子受体的亚细胞定位，细胞可以调节细胞内信号转导途径的活性。在秀丽隐杆线虫外阴发育期间，由LIN-7、LIN-2和LIN-10 PDZ结构域蛋白组成的三元复合物将表皮生长因子受体（EGFR）定位于外阴前体细胞（VPC）的基底外侧区室，以允许通过来自锚细胞的诱导性EGF信号有效激活受体。我们已经确定EGFR底物蛋白-8（EPS-8）是EGFR定位复合物的一种新组分，将受体运输与细胞命运规范联系起来。EPS-8表达在原代VPC中上调，在EGFR/RAS/MAPK通路中形成正反馈环。膜相关鸟苷酸激酶LIN-2将EPS-8招募到受体定位复合物中，以将EGFR保留在基底外侧质膜上，从而使原代细胞谱系中的受体活化达到最大化。邻近的次级VPC中低水平的EPS-8导致EGFR的快速降解，使这些细胞能够采用次级细胞命运。因此，细胞外信号以细胞类型特异性方式调节EGFR运输，以控制器官发生期间的模式形成。
By controlling the subcellular localization of growth factor receptors, cells can modulate the activity of intracellular signal transduction pathways. During Caenorhabditis elegans vulval development, a ternary complex consisting of the LIN‐7, LIN‐2 and LIN‐10 PDZ domain proteins localizes the epidermal growth factor receptor (EGFR) to the basolateral compartment of the vulval precursor cells (VPCs) to allow efficient receptor activation by the inductive EGF signal from the anchor cell. We have identified EGFR substrate protein‐8 (EPS‐8) as a novel component of the EGFR localization complex that links receptor trafficking to cell fate specification. EPS‐8 expression is upregulated in the primary VPCs, where it creates a positive feedback loop in the EGFR/RAS/MAPK pathway. The membrane‐associated guanylate kinase LIN‐2 recruits EPS‐8 into the receptor localization complex to retain the EGFR on the basolateral plasma membrane, and thus allow maximal receptor activation in the primary cell lineage. Low levels of EPS‐8 in the neighboring secondary VPCs result in the rapid degradation of the EGFR, allowing these cells to adopt the secondary cell fate. Extracellular signals thus regulate EGFR trafficking in a cell type‐specific manner to control pattern formation during organogenesis.
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