Vps501, a novel vacuolar SNX-BAR protein cooperates with the SEA complex to regulate TORC1 signaling.

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Traffic Pub Date : 2022-01-30 DOI:10.1111/tra.12833
Shreya Goyal, Verónica A Segarra, Nitika, Aaron M Stetcher, Andrew W Truman, Adam M Reitzel, Richard J Chi
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引用次数: 0

Abstract

The sorting nexins (SNX), constitute a diverse family of molecules that play varied roles in membrane trafficking, cell signaling, membrane remodeling, organelle motility and autophagy. In particular, the SNX-BAR proteins, a SNX subfamily characterized by a C-terminal dimeric Bin/Amphiphysin/Rvs (BAR) lipid curvature domain and a conserved Phox-homology domain, are of great interest. In budding yeast, many SNX-BARs proteins have well-characterized endo-vacuolar trafficking roles. Phylogenetic analyses allowed us to identify an additional SNX-BAR protein, Vps501, with a novel endo-vacuolar role. We report that Vps501 uniquely localizes to the vacuolar membrane and has physical and genetic interactions with the SEA complex to regulate TORC1 inactivation. We found cells displayed a severe deficiency in starvation-induced/nonselective autophagy only when SEA complex subunits are ablated in combination with Vps501, indicating a cooperative role with the SEA complex during TORC1 signaling during autophagy induction. Additionally, we found the SEACIT complex becomes destabilized in vps501Δsea1Δ cells, which resulted in aberrant endosomal TORC1 activity and subsequent Atg13 hyperphosphorylation. We have also discovered that the vacuolar localization of Vps501 is dependent upon a direct interaction with Sea1 and a unique lipid binding specificity that is also required for its function. This article is protected by copyright. All rights reserved.

Abstract Image

Abstract Image

Abstract Image

新型液泡 SNX-BAR 蛋白 Vps501 与 SEA 复合物合作调节 TORC1 信号。
分选蛋白(SNX)是一个多样化的分子家族,在膜贩运、细胞信号传导、膜重塑、细胞器运动和自噬中发挥着不同的作用。其中,SNX-BAR 蛋白是一个 SNX 亚家族,其特征是 C 端有一个二聚 Bin/Amphiphysin/Rvs (BAR)脂质弯曲结构域和一个保守的 Phox 同源结构域。在芽殖酵母中,许多 SNX-BARs 蛋白都具有表征明确的内腔贩运作用。通过系统发育分析,我们发现了另一种 SNX-BAR 蛋白--Vps501,它具有新的内泡作用。我们报告说,Vps501 独特地定位在液泡膜上,并与 SEA 复合物发生物理和基因相互作用,以调节 TORC1 的失活。我们发现,只有当 SEA 复合物亚基与 Vps501 一起被消减时,细胞才会显示出饥饿诱导/非选择性自噬的严重缺陷,这表明在自噬诱导过程中,SEA 复合物在 TORC1 信号传导过程中起着合作作用。此外,我们还发现 SEACIT 复合物在 vps501Δsea1Δ 细胞中变得不稳定,从而导致内体 TORC1 活性失常和随后的 Atg13 过度磷酸化。我们还发现,Vps501的液泡定位依赖于与Sea1的直接相互作用以及其功能所需的独特脂质结合特异性。本文受版权保护。保留所有权利。
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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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