Olivares-Castiñeira Ivette, Llimargas Marta
Developmental Biology Department, Institut de Biologia Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Barcelona, Spain.
PLoS Genet. 2017 Jul 5;13(7):e1006882. doi: 10.1371/journal.pgen.1006882. eCollection 2017 Jul.
Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length. EGFR regulates the organisation of endosomes in which Crb and Serp proteins are loaded. Our results are consistent with a role of EGFR in regulating Retromer/WASH recycling routes. Furthermore, we provide new insights into Crb trafficking and recycling during organ formation. Our work connects cell signalling, trafficking mechanisms and morphogenesis and suggests that the regulation of cargo trafficking can be a general outcome of EGFR activation.
发育受少数保守的信号通路调控。其中，表皮生长因子受体（EGFR）通路反复用于器官和组织的形成，一旦失调，可能导致癌症和转移。鉴于其相关性，识别其下游分子机制并了解其如何指导细胞变化至关重要。在这里，我们在果蝇的呼吸系统中探讨这个问题。我们发现EGFR在限制气管背干伸长方面具有新作用。我们发现EGFR调节顶端决定因子Crb和细胞外基质调节因子Serp，这两个因子此前已知可控制管的长度。EGFR调节内体的组织，Crb和Serp蛋白在内体中装载。我们的结果与EGFR在调节Retromer/WASH回收途径中的作用一致。此外，我们对器官形成过程中Crb的运输和再循环提供了新的见解。我们的工作将细胞信号传导、运输机制和形态发生联系起来，并表明货物运输的调节可能是EGFR激活的普遍结果。
