小柯机器人

美国哈佛医学院Norbert Perrimon等研究人员合作发现，一种磷酸盐感应细胞器调节磷酸盐和组织的平衡状态。2023年5月3日，国际知名学术期刊《自然》在线发表了这一成果。

在观察到慢性无机磷酸盐（P_i）饥饿导致黑腹果蝇消化道上皮细胞过度增殖后，研究人员确定P_i饥饿会触发P_i转运体PXo的下调。与P_i饥饿一致，PXo的缺乏导致中肠的过度增殖。有趣的是，免疫染色和超微结构分析显示，PXo专门标记非经典多细胞器（PXo体）。此外，通过使用基于福斯特共振能量转移（FRET）的P_i传感器进行P_i成像，研究人员发现PXo限制了细胞内的P_i水平。PXo体需要PXo进行生物生成，并在P_i饥饿后发生降解。PXo体的蛋白质组和脂质组特征揭示了其作为细胞内P_i储备的独特特征。因此，P_i饥饿会触发PXo下调和PXo体降解，作为增加细胞膜P_i的补偿机制。

最后，研究人员确定了STRIPAK复合体和JNK信号的组成部分，即AP-1（Cka）的激酶连接器，作为PXo敲除或P_i饥饿诱导的过度增殖的媒介。总的来说，这项研究发现PXo体是细胞膜P_i水平的一个重要调节器，并确定了一个P_i依赖性的PXo-Cka-JNK信号级联，控制着组织的稳态。

据介绍，P_i是生命的重要分子之一。然而，人们对动物组织中的细胞内P_i代谢和信号传递知之甚少。

附：英文原文

Title: A phosphate-sensing organelle regulates phosphate and tissue homeostasis

Author: Xu, Chiwei, Xu, Jun, Tang, Hong-Wen, Ericsson, Maria, Weng, Jui-Hsia, DiRusso, Jonathan, Hu, Yanhui, Ma, Wenzhe, Asara, John M., Perrimon, Norbert

Issue&Volume: 2023-05-03

Abstract: Inorganic phosphate (Pi) is one of the essential molecules for life. However, little is known about intracellular Pi metabolism and signalling in animal tissues1. Following the observation that chronic Pi starvation causes hyperproliferation in the digestive epithelium of Drosophila melanogaster, we determined that Pi starvation triggers the downregulation of the Pi transporter PXo. In line with Pi starvation, PXo deficiency caused midgut hyperproliferation. Interestingly, immunostaining and ultrastructural analyses showed that PXo specifically marks non-canonical multilamellar organelles (PXo bodies). Further, by Pi imaging with a Frster resonance energy transfer (FRET)-based Pi sensor2, we found that PXo restricts cytosolic Pi levels. PXo bodies require PXo for biogenesis and undergo degradation following Pi starvation. Proteomic and lipidomic characterization of PXo bodies unveiled their distinct feature as an intracellular Pi reserve. Therefore, Pi starvation triggers PXo downregulation and PXo body degradation as a compensatory mechanism to increase cytosolic Pi. Finally, we identified connector of kinase to AP-1 (Cka), a component of the STRIPAK complex and JNK signalling3, as the mediator of PXo knockdown- or Pi starvation-induced hyperproliferation. Altogether, our study uncovers PXo bodies as a critical regulator of cytosolic Pi levels and identifies a Pi-dependent PXo–Cka–JNK signalling cascade controlling tissue homeostasis.

DOI: 10.1038/s41586-023-06039-y

Source: https://www.nature.com/articles/s41586-023-06039-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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