Goyal Shreya, Segarra Verónica A, Stetcher Aaron M, Truman Andrew W, Reitzel Adam M, Chi Richard J
Department of Biological Sciences, University of North Carolina, Charlotte, USA.
Department of Biology, High Point University, High Point, NC, USA.
Traffic. 2022 Jan 30;23(4):192-207. doi: 10.1111/tra.12833.
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.
分选连接蛋白（SNX）构成了一个多样化的分子家族，它们在膜运输、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。特别是，SNX-BAR蛋白是SNX的一个亚家族，其特征是具有一个C端二聚体Bin/Amphiphysin/Rvs（BAR）脂质曲率结构域和一个保守的Phox同源结构域，备受关注。在出芽酵母中，许多SNX-BAR蛋白在内体-液泡运输中具有明确的作用。系统发育分析使我们能够鉴定出一种额外的SNX-BAR蛋白Vps501，它在内体-液泡中具有新的作用。我们报告称，Vps501独特地定位于液泡膜，并与SEA复合物存在物理和遗传相互作用，以调节TORC1失活。我们发现，只有当SEA复合物亚基与Vps501一起被敲除时，细胞在饥饿诱导的/非选择性自噬中才表现出严重缺陷，这表明在自噬诱导过程中TORC1信号传导期间，它与SEA复合物具有协同作用。此外，我们发现SEACIT复合物在vps501Δsea1Δ细胞中变得不稳定，这导致异常的内体TORC1活性和随后的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。
