NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development.
NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development.
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DOI：
10.1093/g3journal/jkad013
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发表时间：
2023-03-09
影响因子：
2.6
通讯作者：
Poon, Carole
中科院分区：
文献类型：
--
作者：
Hudson, Joshua;Paul, Sayantanee;Veraksa, Alexey;Ghabrial, Amin;Harvey, Kieran F.;Poon, Carole
生发中心激酶III(Gck III)通路是一个类似河马的激酶模块，由Ste20激酶TO和Gck III依次激活，然后是核DBF2相关(NDR)激酶三角化(TRC)。我们之前发现了Gck III通路在果蝇气管(呼吸)管形态中的作用。气管形成对氧气运输至关重要的分支上皮管网络，在结构上类似于脊椎动物的分支管状器官，如血管系统。在缺乏Gck III途径功能的情况下，气管内会形成以连接蛋白和顶端蛋白错位为特征的异常扩张，这表明该途径在维持气管发育过程中的完整性方面起着重要作用。在这里，我们观察到TRC和脑海绵状血管畸形3(Ccm3)之间的遗传相互作用，Ccm3是人类血管疾病基因的果蝇同源基因，支持我们的假设，即Gck III通路在Ccm3下游的气管中发挥作用，并可能在脊椎动物的脑血管系统中发挥作用。然而，Gck III信号通路是如何调控的，以及其在气管发育中的作用机制尚不清楚。我们采用了生化和遗传学的方法来识别与TRC相互作用的蛋白质，TRC是最下游的Gck III途径激酶。我们发现，已知的Gck III和NDR支架蛋白可能在气管发育中控制Gck III途径信号转导，这与它们在河马样模块中的保守作用一致。此外，我们还显示了TRC和多种酶在糖酵解和氧化磷酸化过程中的遗传相互作用，表明Gck III途径在整合细胞能量需求和维持管子完整性方面具有潜在的功能。
The Germinal Center Kinase III (GckIII) pathway is a Hippo-like kinase module defined by sequential activation of Ste20 kinases Thousand and One (Tao) and GckIII, followed by nuclear dbf2-related (NDR) kinase Tricornered (Trc). We previously uncovered a role for the GckIII pathway in Drosophila melanogaster tracheal (respiratory) tube morphology. The trachea form a network of branched epithelial tubes essential for oxygen transport, and are structurally analogous to branched tubular organs in vertebrates, such as the vascular system. In the absence of GckIII pathway function, aberrant dilations form in tracheal tubes characterized by mislocalized junctional and apical proteins, suggesting that the pathway is important in maintaining tube integrity in development. Here, we observed a genetic interaction between trc and Cerebral cavernous malformations 3 (Ccm3), the Drosophila ortholog of a human vascular disease gene, supporting our hypothesis that the GckIII pathway functions downstream of Ccm3 in trachea, and potentially in the vertebrate cerebral vasculature. However, how GckIII pathway signaling is regulated and the mechanisms that underpin its function in tracheal development are unknown. We undertook biochemical and genetic approaches to identify proteins that interact with Trc, the most downstream GckIII pathway kinase. We found that known GckIII and NDR scaffold proteins are likely to control GckIII pathway signaling in tracheal development, consistent with their conserved roles in Hippo-like modules. Furthermore, we show genetic interactions between trc and multiple enzymes in glycolysis and oxidative phosphorylation, suggesting a potential function of the GckIII pathway in integrating cellular energy requirements with maintenance of tube integrity.
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DOI：
10.1016/j.str.2018.05.014
发表时间：
2018-08-07
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Xiong S;Lorenzen K;Couzens AL;Templeton CM;Rajendran D;Mao DYL;Juang YC;Chiovitti D;Kurinov I;Guettler S;Gingras AC;Sicheri F
通讯作者：
Sicheri F
影响因子：
64.5
作者：
Emoto, K;He, Y;Jan, YN
通讯作者：
Jan, YN
影响因子：
4.8
作者：
Cansby, Emmelie;Kulkarni, Nagaraj M.;Mahlapuu, Margit
通讯作者：
Mahlapuu, Margit
影响因子：
4.8
作者：
Devroe, E;Erdjument-Bromage, H;Silver, PA
通讯作者：
Silver, PA
影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter