Gauthier Kimberley, Rocheleau Christian E
Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.
Methods Mol Biol. 2017;1652:43-61. doi: 10.1007/978-1-4939-7219-7_3.
Epidermal growth factor receptor (EGFR)-mediated activation of the canonical Ras/MAPK signaling cascade is responsible for cell proliferation and cell growth. This signaling pathway is frequently overactivated in epithelial cancers; therefore, studying regulation of this pathway is crucial not only for our fundamental understanding of cell biology but also for our ability to treat EGFR-related disease. Genetic model organisms such as Caenorhabditis elegans, a hermaphroditic nematode, played a vital role in identifying components of the EGFR/Ras/MAPK pathway and delineating their order of function, and continues to play a role in identifying novel regulators of the pathway. Polarized activation of LET-23, the C. elegans homolog of EGFR, is responsible for induction of the vulval cell fate; perturbations in this signaling pathway produce either a vulvaless or multivulva phenotype. The translucent cuticle of the nematode facilitates in vivo visualization of the receptor, revealing that localization of LET-23 EGFR is tightly regulated and linked to its function. In this chapter, we review the methods used to harness vulva development as a tool for studying EGFR signaling and trafficking in C. elegans.
表皮生长因子受体(EGFR)介导的经典Ras/丝裂原活化蛋白激酶(MAPK)信号级联激活负责细胞增殖和细胞生长。该信号通路在上皮癌中经常过度激活;因此,研究该通路的调控不仅对于我们对细胞生物学的基本理解至关重要,而且对于我们治疗EGFR相关疾病的能力也至关重要。遗传模式生物,如秀丽隐杆线虫(一种雌雄同体的线虫),在鉴定EGFR/Ras/MAPK通路的组成部分并确定其功能顺序方面发挥了至关重要的作用,并且在鉴定该通路的新型调节因子方面继续发挥作用。LET-23(EGFR的秀丽隐杆线虫同源物)的极化激活负责诱导外阴细胞命运;该信号通路的扰动会产生无外阴或多外阴表型。线虫的半透明角质层便于在体内观察受体,表明LET-23 EGFR的定位受到严格调控并与其功能相关。在本章中,我们回顾了利用外阴发育作为研究秀丽隐杆线虫中EGFR信号传导和运输工具的方法。