The TSC1/2 complex controls Drosophila pigmentation through TORC1-dependent regulation of catecholamine biosynthesis.
The TSC1/2 complex controls Drosophila pigmentation through TORC1-dependent regulation of catecholamine biosynthesis.
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DOI：
10.1371/journal.pone.0048720
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Roegiers F
中科院分区：
文献类型：
--
作者：
Zitserman D;Gupta S;Kruger WD;Karbowniczek M;Roegiers F
在果蝇中，成体色素沉着的模式是在蛹后期由儿茶酚胺多巴和多巴胺的产生而开始的，儿茶酚胺多巴和多巴胺转化为黑色素。黑色素沉积的模式和程度受黑檀木和黄色等基因的表达以及参与儿茶酚胺生物合成的酶的控制。在这项研究中，我们发现保守的TSC/TORC1细胞生长通路控制着果蝇色素沉着过程中儿茶酚胺的生物合成。我们发现，高水平的Rheb （TORC1复合体的激活剂）促进蛹期机械感觉刚毛的过早色素沉着，并改变成年果蝇角质层的色素沉着。通过RNAi敲低酪氨酸羟化酶（TH）等黑色素生成酶来破坏黑色素合成，或通过Raptor敲低TORC1活性来抑制体内rheb依赖性色素沉着表型。Rheb活性的增加通过增加表皮细胞中TH的水平来驱动色素沉着。我们的研究结果表明，通过调节黑色素形成过程中一种关键酶的水平，色素沉着的控制与细胞营养感知途径有关，这进一步证明了TORC1的不适当激活可以以意想不到的方式改变代谢和分化途径。TORC1是人类结节性硬化症复杂肿瘤综合征的标志。
In Drosophila, the pattern of adult pigmentation is initiated during late pupal stages by the production of catecholamines DOPA and dopamine, which are converted to melanin. The pattern and degree of melanin deposition is controlled by the expression of genes such as ebony and yellow as well as by the enzymes involved in catecholamine biosynthesis. In this study, we show that the conserved TSC/TORC1 cell growth pathway controls catecholamine biosynthesis in Drosophila during pigmentation. We find that high levels of Rheb, an activator of the TORC1 complex, promote premature pigmentation in the mechanosensory bristles during pupal stages, and alter pigmentation in the cuticle of the adult fly. Disrupting either melanin synthesis by RNAi knockdown of melanogenic enzymes such as tyrosine hydroxylase (TH), or downregulating TORC1 activity by Raptor knockdown, suppresses the Rheb-dependent pigmentation phenotype in vivo. Increased Rheb activity drives pigmentation by increasing levels of TH in epidermal cells. Our findings indicate that control of pigmentation is linked to the cellular nutrient-sensing pathway by regulating levels of a critical enzyme in melanogenesis, providing further evidence that inappropriate activation of TORC1, a hallmark of the human tuberous sclerosis complex tumor syndrome disorder, can alter metabolic and differentiation pathways in unexpected ways.
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DOI：
10.1083/jcb.201103018
发表时间：
2011-05-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amcheslavsky A;Ito N;Jiang J;Ip YT
通讯作者：
Ip YT
影响因子：
3.3
作者：
Tong X;Zitserman D;Serebriiskii I;Andrake M;Dunbrack R;Roegiers F
通讯作者：
Roegiers F
影响因子：
56.9
作者：
Dorrello, N. Valerio;Peschiaroli, Angelo;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
9.2
作者：
True, JR;Edwards, KA;Carroll, SB
通讯作者：
Carroll, SB
影响因子：
64.5
作者：
Ito, N;Rubin, GM
通讯作者：
Rubin, GM