美国德克萨斯大学西南医学中心Peter M Douglas研究组发现小G蛋白香叶酰化可监测细胞内脂质稳态。2022年5月18日出版的《自然》杂志发表了这项成果。

他们描述了一种在秀丽隐杆线虫中进行细胞内脂质监测的机制，该机制涉及核激素受体 NHR-49 的转录失活，其通过与小 G 蛋白 RAB-11.1 结合的香叶基香叶酯结合到内吞囊泡进行胞质隔离。由脂质消耗引起的有缺陷的从头类异戊二烯合成限制了 RAB-11.1 香叶基香叶酰化，这促进了 NHR-49 的核易位和 rab-11.2 转录的激活，以增强转运蛋白在质膜上的驻留。因此，他们鉴定了一种细胞可感知的关键脂质，及与其相连 G 蛋白和核受体，它们的动态相互作用使细胞能够感知由于脂质消耗引起的代谢需求，并通过增加营养吸收和脂质代谢来做出反应。

据悉，脂质稳态失衡会对健康产生有害影响。然而，细胞如何感知由于脂质消耗导致的代谢需求并通过增加营养吸收做出反应仍不清楚。

附：英文原文

Title: Intracellular lipid surveillance by small G protein geranylgeranylation

Author: Watterson, Abigail, Tatge, Lexus, Wajahat, Naureen, Arneaud, Sonja L. B., Solano Fonseca, Rene, Beheshti, Shaghayegh T., Metang, Patrick, Mihelakis, Melina, Zuurbier, Kielen R., Corley, Chase D., Dehghan, Ishmael, McDonald, Jeffrey G., Douglas, Peter M.

Issue&Volume: 2022-05-18

Abstract: Imbalances in lipid homeostasis can have deleterious effects on health1,2. Yet how cells sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption remains unclear. Here we describe a mechanism for intracellular lipid surveillance in Caenorhabditis elegans that involves transcriptional inactivation of the nuclear hormone receptor NHR-49 through its cytosolic sequestration to endocytic vesicles via geranylgeranyl conjugation to the small G protein RAB-11.1. Defective de novo isoprenoid synthesis caused by lipid depletion limits RAB-11.1 geranylgeranylation, which promotes nuclear translocation of NHR-49 and activation of rab-11.2 transcription to enhance transporter residency at the plasma membrane. Thus, we identify a critical lipid sensed by the cell, its conjugated G protein, and the nuclear receptor whose dynamic interactions enable cells to sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption and lipid metabolism. In Caenorhabditis elegans, geranylgeranyl conjugation to RAB-11.1 acts as a lipid sensor to regulate nutrient uptake and lipid metabolism in response to metabolic demand.

DOI: 10.1038/s41586-022-04729-7

Source: https://www.nature.com/articles/s41586-022-04729-7