The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.
The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.
复制标题
DOI：
10.1371/journal.pone.0010245
复制
发表时间：
2010-04-21
期刊：
影响因子：
3.7
通讯作者：
Affolter M
中科院分区：
文献类型：
--
作者：
Chanut-Delalande H;Jung AC;Baer MM;Lin L;Payre F;Affolter M
内吞作用是多种信号传导途径的关键调节步骤，包括受体酪氨酸激酶（RTK）信号传导。Hrs和Stam构成ESCRT-0复合物，其控制泛素化蛋白的初始选择，随后将在溶酶体中降解。它已被很好地建立离体和在果蝇胚胎发育过程中，Hrs促进EGFR下调。我们最近分离出了苍蝇中Stam的第一个突变，并表明Stam是气囊形态发生所需的，气囊是一种幼虫呼吸结构，其形成关键取决于FGFR活性的微调水平。这表明Stam，ESCRT-0复合物中的puridine，调节FGF信号传导，这一可能性尚未在果蝇中研究。在这里，我们评估的作用的HRS/Stam复杂的调节信号活动在果蝇的发展。我们发现，在气管系统中，无论是在气囊原基的细胞迁移过程中，并在终端细胞的精细细胞质延伸的形成过程中，需要有效的FGFR信号。我们发现，fGFR和hrs突变细胞显示改变的FGFR/Btl定位，可能有助于受损的信号传导水平。电子显微镜分析表明，内体成熟受损，在不同的步骤hrs和hrs突变。这些有些出乎意料的结果促使我们进一步探索EGFR信号传导中的EGFR和hrs的功能。我们发现，虽然在胚胎中，EGFR和hrs一起下调EGFR信号，但它们是翅膀发育过程中EGFR信号完全激活所必需的。我们的研究表明，ESCRT-0复合物差异调节RTK信号，无论是积极或消极的组织和发育阶段，进一步强调了在发育过程中调节信号通路的内吞作用的重要性。
Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK) signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.
登录
查看更多内容
影响因子：
10.5
作者：
KLAMBT, C;GLAZER, L;SHILO, BZ
通讯作者：
SHILO, BZ
DOI：
10.1016/j.bbrc.2003.08.078
发表时间：
2003-10-03
影响因子：
3.1
作者：
Kanazawa, C;Morita, E;Sugamura, K
通讯作者：
Sugamura, K
DOI：
10.1016/j.bbrc.2006.10.068
发表时间：
2006-12-22
影响因子：
3.1
作者：
Kim, Man Su;Kim, Jeom-A;Jeon, Hyesung
通讯作者：
Jeon, Hyesung
影响因子：
7.7
作者：
Jékely, G;Rorth, P
通讯作者：
Rorth, P
影响因子：
4.8
作者：
Bache, KG;Raiborg, C;Stenmark, H
通讯作者：
Stenmark, H