The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size.
The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size.
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DOI：
10.7554/elife.81170
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发表时间：
2023-05-05
期刊：
影响因子：
7.7
通讯作者：
Henne WM
中科院分区：
文献类型：
--
作者：
Ugrankar-Banerjee R;Tran S;Bowerman J;Kovalenko A;Paul B;Henne WM
营养储存缺陷和脂肪细胞增大（肥大）是代谢综合征和2型糖尿病的新特征。在脂肪组织中，细胞骨架网络如何影响脂肪细胞大小、营养摄取、脂肪储存和信号传导仍然知之甚少。利用果蝇幼虫脂肪体（FB）作为模型脂肪组织，我们表明，一个特定的肌动蛋白亚型-Act 5C-形式的皮质肌动蛋白网络所需的扩大脂肪细胞的大小，在发展中的生物量存储。此外，我们发现了一个非典型的作用，皮质肌动蛋白细胞骨架在器官间的脂质运输。我们发现Act 5C定位于FB细胞表面和细胞-细胞边界，在那里它密切接触外周LD（PLD），形成一个皮质肌动蛋白网络，用于细胞结构支持。FB-特异性Act 5C损失扰乱FB甘油三酯（TG）储存和LD形态，导致发育延迟的幼虫不能发育成蝇。利用时间RNAi耗尽的方法，我们揭示了Act 5C是不可缺少的后胚胎发育过程中的幼虫喂养FB细胞扩大和储存脂肪。Act 5C缺陷型FB不能生长，导致脂肪营养不良的幼虫不能积累足够的生物量用于完全变态。与此相一致，Act 5C缺陷的幼虫显示出胰岛素信号转导减弱和摄食减少。从机制上讲，我们还表明这种减少的信号传导与减少的载脂蛋白（Lpp）脂蛋白介导的脂质转运相关，并发现Act 5C是Lpp从FB分泌进行脂质转运所必需的。总的来说，我们提出，果蝇脂肪组织的Act 5C依赖的皮质肌动蛋白网络是必需的脂肪组织的大小扩张和生物体能量稳态的发展，并发挥重要作用，在器官间的营养运输和信号。
Defective nutrient storage and adipocyte enlargement (hypertrophy) are emerging features of metabolic syndrome and type 2 diabetes. Within adipose tissues, how the cytoskeletal network contributes to adipose cell size, nutrient uptake, fat storage, and signaling remain poorly understood. Utilizing the Drosophila larval fat body (FB) as a model adipose tissue, we show that a specific actin isoform—Act5C—forms the cortical actin network necessary to expand adipocyte cell size for biomass storage in development. Additionally, we uncover a non-canonical role for the cortical actin cytoskeleton in inter-organ lipid trafficking. We find Act5C localizes to the FB cell surface and cell-cell boundaries, where it intimately contacts peripheral LDs (pLDs), forming a cortical actin network for cell architectural support. FB-specific loss of Act5C perturbs FB triglyceride (TG) storage and LD morphology, resulting in developmentally delayed larvae that fail to develop into flies. Utilizing temporal RNAi-depletion approaches, we reveal that Act5C is indispensable post-embryogenesis during larval feeding as FB cells expand and store fat. Act5C-deficient FBs fail to grow, leading to lipodystrophic larvae unable to accrue sufficient biomass for complete metamorphosis. In line with this, Act5C-deficient larvae display blunted insulin signaling and reduced feeding. Mechanistically, we also show this diminished signaling correlates with decreased lipophorin (Lpp) lipoprotein-mediated lipid trafficking, and find Act5C is required for Lpp secretion from the FB for lipid transport. Collectively, we propose that the Act5C-dependent cortical actin network of Drosophila adipose tissue is required for adipose tissue size-expansion and organismal energy homeostasis in development, and plays an essential role in inter-organ nutrient transport and signaling.
影响因子：
3.7
作者：
Suh JM;Stenesen D;Peters JM;Inoue A;Cade A;Graff JM
通讯作者：
Graff JM
DOI：
10.1016/j.bbrc.2012.08.028
发表时间：
2012-09-14
影响因子：
3.1
作者：
Sassu, Eric D.;McDermott, Jacqueline E.;Keys, Brendan J.;Esmaeili, Melody;Keene, Alex C.;Birnbaum, Morris J.;DiAngelo, Justin R.
通讯作者：
DiAngelo, Justin R.