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介导蛋白质从ER靶向脂滴两种途径的鉴定
作者:小柯机器人 发布时间:2022/9/3 22:12:35

美国哈佛医学院Tobias C. Walther和Robert V. Farese Jr.研究组合作鉴定了介导蛋白质从ER靶向脂滴的两种途径。该项研究成果发表在2022年9月1日出版的《自然—细胞生物学》上。

他们确定了两种不同的ER-to-LD蛋白质靶向途径:在形成过程中早期靶向LD形成位点,以及在形成后晚期靶向成熟LD。在果蝇细胞中使用系统、公正的方法,他们确定了晚期靶向途径所需的特定膜融合机制,包括调节剂、系链和SNARE 蛋白。这种融合机器的组件定位于LD-ER界面并在ER出口处组织。他们为早期和晚期ER-to-LD靶向途径确定了多种货物。他们的研究结果提供了一个模型,说明蛋白质如何在LD形成期间或通过蛋白质催化的膜桥形成从ER靶向LD。

据了解,将蛋白质定位到其作用位点的途径对于真核细胞的组织和功能至关重要。尽管已经定义了蛋白质靶向许多细胞器的机制,但人们对蛋白质如代谢酶如何从内质网(ER)靶向细胞脂滴(LD)知之甚少。

附:英文原文

Title: Identification of two pathways mediating protein targeting from ER to lipid droplets

Author: Song, Jiunn, Mizrak, Arda, Lee, Chia-Wei, Cicconet, Marcelo, Lai, Zon Weng, Tang, Wei-Chun, Lu, Chieh-Han, Mohr, Stephanie E., Farese, Robert V., Walther, Tobias C.

Issue&Volume: 2022-09-01

Abstract: Pathways localizing proteins to their sites of action are essential for eukaryotic cell organization and function. Although mechanisms of protein targeting to many organelles have been defined, how proteins, such as metabolic enzymes, target from the endoplasmic reticulum (ER) to cellular lipid droplets (LDs) is poorly understood. Here we identify two distinct pathways for ER-to-LD protein targeting: early targeting at LD formation sites during formation, and late targeting to mature LDs after their formation. Using systematic, unbiased approaches in Drosophila cells, we identified specific membrane-fusion machinery, including regulators, a tether and SNARE proteins, that are required for the late targeting pathway. Components of this fusion machinery localize to LD–ER interfaces and organize at ER exit sites. We identified multiple cargoes for early and late ER-to-LD targeting pathways. Our findings provide a model for how proteins target to LDs from the ER either during LD formation or by protein-catalysed formation of membrane bridges.

DOI: 10.1038/s41556-022-00974-0

Source: https://www.nature.com/articles/s41556-022-00974-0

期刊信息

Nature Cell Biology:《自然—细胞生物学》,创刊于1999年。隶属于施普林格·自然出版集团,最新IF:20.042
官方网址:https://www.nature.com/ncb/
投稿链接:https://mts-ncb.nature.com/cgi-bin/main.plex