Golgi screen identifies the RhoGEF Solo as a novel regulator of RhoB and endocytic transport.

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Traffic Pub Date : 2023-04-01 DOI:10.1111/tra.12880
Cristiana Lungu, Florian Meyer, Marcel Hörning, Jasmin Steudle, Anja Braun, Bettina Noll, David Benz, Felix Fränkle, Simone Schmid, Stephan A Eisler, Monilola A Olayioye
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引用次数: 2

Abstract

The control of intracellular membrane trafficking by Rho GTPases is central to cellular homeostasis. How specific guanine nucleotide exchange factors and GTPase-activating proteins locally balance GTPase activation in this process is nevertheless largely unclear. By performing a microscopy-based RNAi screen, we here identify the RhoGEF protein Solo as a functional counterplayer of DLC3, a RhoGAP protein with established roles in membrane trafficking. Biochemical, imaging and optogenetics assays further uncover Solo as a novel regulator of endosomal RhoB. Remarkably, we find that Solo and DLC3 control not only the activity, but also total protein levels of RhoB in an antagonistic manner. Together, the results of our study uncover the first functionally connected RhoGAP-RhoGEF pair at endomembranes, placing Solo and DLC3 at the core of endocytic trafficking.

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高尔基筛检发现RhoGEF Solo是RhoB和内吞运输的一种新型调节剂。
Rho GTPases对细胞膜内运输的控制是细胞稳态的核心。特异的鸟嘌呤核苷酸交换因子和GTPase激活蛋白如何在这个过程中局部平衡GTPase激活,目前还不清楚。通过进行基于显微镜的RNAi筛选,我们在这里鉴定了RhoGEF蛋白Solo作为DLC3的功能对抗者,DLC3是一种RhoGAP蛋白,在膜运输中具有确定的作用。生化、成像和光遗传学分析进一步揭示Solo是内体RhoB的一种新的调节因子。值得注意的是,我们发现Solo和DLC3不仅以拮抗方式控制RhoB的活性,而且还以拮抗方式控制RhoB的总蛋白水平。总之,我们的研究结果揭示了第一个在内膜上功能连接的RhoGAP-RhoGEF对,将Solo和DLC3置于内吞运输的核心。
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来源期刊
Traffic
Traffic 生物-细胞生物学
CiteScore
8.10
自引率
2.20%
发文量
50
审稿时长
2 months
期刊介绍: Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.
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