Compensatory flux changes within an endocytic trafficking network maintain thermal robustness of Notch signaling.
Compensatory flux changes within an endocytic trafficking network maintain thermal robustness of Notch signaling.
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DOI：
10.1016/j.cell.2014.03.050
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发表时间：
2014-05-22
期刊：
影响因子：
64.5
通讯作者：
Baron M
中科院分区：
文献类型：
--
作者：
Shimizu H;Woodcock SA;Wilkin MB;Trubenová B;Monk NA;Baron M
发育信号对包括温度在内的环境变化非常敏感。例如，在变温动物如果蝇中，Notch信号传导在宽温度范围内保持在功能限制内。我们结合联合收割机的实验和计算的方法来表明，Notch信号的温度补偿是通过一个意想不到的各种内吞依赖的途径Notch激活，当叠加在配体诱导的激活，作为一个鲁棒性模块。热补偿通过改变竞争运输路线内的流量平衡而产生，再加上Notch的温度依赖性泛素化。这种灵活的运输途径集合在低温下支持Notch信号传导，但可以在高温下切换以抑制Notch信号传导，从而补偿配体诱导的活化的固有温度敏感性。其结果是扩大了正常发育的生理范围。类似的机制可以为其他发育信号提供热鲁棒性。Notch激活有多种途径受温度不同影响Dx和Su（dx）促进网格蛋白依赖性和非依赖性Notch内吞Notch内吞通过不同途径可上调或下调信号转导内吞网络内的通量变化确保Notch信号对温度的鲁棒性在果蝇发育期间Notch信号对温度变化的鲁棒性是通过竞争性温度网络实现的。依赖的内吞运输途径。这些稳定的信号水平，在面对温度变化，影响配体诱导的受体活化。
Developmental signaling is remarkably robust to environmental variation, including temperature. For example, in ectothermic animals such as Drosophila, Notch signaling is maintained within functional limits across a wide temperature range. We combine experimental and computational approaches to show that temperature compensation of Notch signaling is achieved by an unexpected variety of endocytic-dependent routes to Notch activation which, when superimposed on ligand-induced activation, act as a robustness module. Thermal compensation arises through an altered balance of fluxes within competing trafficking routes, coupled with temperature-dependent ubiquitination of Notch. This flexible ensemble of trafficking routes supports Notch signaling at low temperature but can be switched to restrain Notch signaling at high temperature and thus compensates for the inherent temperature sensitivity of ligand-induced activation. The outcome is to extend the physiological range over which normal development can occur. Similar mechanisms may provide thermal robustness for other developmental signals. There are multiple routes to Notch activation, differently affected by temperature Dx and Su(dx) promote clathrin-dependent and -independent Notch endocytosis Notch endocytosis through the distinct routes can up- or downregulate signaling Flux changes within endocytic network ensure Notch signal is robust to temperature The robustness of Notch signaling to temperature changes during fly development is achieved by a network of competing temperature-dependent endocytic trafficking routes. These stabilize signaling levels in the face of temperature variation that influences ligand-induced receptor activation.
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DOI：
10.1074/jbc.m112.428854
发表时间：
2013-03-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Whiteman P;de Madrid BH;Taylor P;Li D;Heslop R;Viticheep N;Tan JZ;Shimizu H;Callaghan J;Masiero M;Li JL;Banham AH;Harris AL;Lea SM;Redfield C;Baron M;Handford PA
通讯作者：
Handford PA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.9
作者：
Levental, Ilya;Grzybek, Michal;Simons, Kai
通讯作者：
Simons, Kai
影响因子：
4
作者：
Fortini, Mark E.;Bilder, David
通讯作者：
Bilder, David
影响因子：
4
作者：
Schneider, Markus;Troost, Tobias;Klein, Thomas
通讯作者：
Klein, Thomas