Pentagone internalises glypicans to fine-tune multiple signalling pathways

Pentagone internalises glypicans to fine-tune multiple signalling pathways
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Pentagone 内化磷脂酰肌醇蛋白聚糖以微调多个信号通路

DOI:
10.7554/elife.13301
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发表时间:
2016
期刊:
影响因子:
7.7
通讯作者:
George Pyrowolakis
George Pyrowolakis
中科院分区:
生物学1区
文献类型:
--
作者:
M. Norman;Robin Vuilleumier;Alexander Springhorn;J. Gawlik;George Pyrowolakis

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信号传导活性的严格调节对于适当的组织图案化和生长至关重要。在这里,我们调查的五角蛋白(Pent),分泌蛋白,在建立和维护BMP/DPP形态发生信号在果蝇翅膀发育过程中的调节反馈的作用的功能。我们表明,Pent内化的DPP共受体,磷脂酰肌醇蛋白Dally和Dally样蛋白(DLP),并提出这种内化是重要的,在建立一个长范围的DPP梯度。戊诱导的内吞作用和降解磷脂酰肌醇蛋白聚糖需要发动蛋白和Rab 5,但不是网格蛋白或活性BMP信号。因此,Pent通过微调质膜上BMP接收系统的水平来改变细胞捕获和固定BMP的能力。此外,根据磷脂酰肌醇蛋白聚糖在多个信号通路中的作用,我们建立了Wg信号传导的Pent要求。我们的数据提出了一种新的机制,形态发生蛋白信号的调节。DOI:http://dx.doi.org/10.7554/eLife.13301.001网站
Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated. DOI: http://dx.doi.org/10.7554/eLife.13301.001
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