Plant ESCRT protein ALIX coordinates with retromer complex in regulating receptor-mediated sorting of soluble vacuolar proteins.

Plant ESCRT protein ALIX coordinates with retromer complex in regulating receptor-mediated sorting of soluble vacuolar proteins.
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植物 ESCRT 蛋白 ALIX 与逆转录体复合物协调调节受体介导的可溶性液泡蛋白分选

DOI:
10.1073/pnas.2200492119
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发表时间:
2022-05-17
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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多细胞生物中的内体转运所需的分选复合物(ESCRT)在多泡体(MVB)生物发生和膜蛋白分选中起着典型的作用。尽管如此,其在可溶性液泡蛋白的分选中的关键作用及其与内体再循环机制的相互作用还有待报道。在这项研究中,我们证明了拟南芥ESCRT相关的ALIX与retromer核心亚基相互作用,以调节其在内体膜上的募集,以回收液泡分选受体(VSR),从而有效地分选可溶性液泡蛋白。这项工作提供了分子的见解阿利克斯在调节液泡运输可溶性蛋白质的独特性质,从而在植物中的液泡运输和内体回收途径之间的串扰和协调提供了新的光。胞膜蛋白在植物生理和发育中起着重要作用,但调节其囊泡通过内膜室运输的因素和机制仍然很大程度上未知。我们和其他人最近已经确定了一个进化上保守的植物内体分选复合物所需的运输(ESCRT)相关的蛋白质与凋亡相关的基因-2相互作用蛋白X(阿利克斯),发挥典型的功能,在生物发生的多泡体/prevacuolar室(MVB/PVC)和泛素化的膜蛋白的排序。在这项研究中,我们阐明了阿利克斯在调节可溶性蛋白质的液泡运输中的作用和潜在机制,超出了其在真核细胞中的传统ESCRT功能。我们表明,阿利克斯共定位和物理相互作用的逆转录核心亚基Vps 26和Vps 29在植物。此外,双突变体分析揭示了阿利克斯与Vps 26和Vps 29的遗传相互作用,用于调节可溶性液泡蛋白的运输。有趣的是,阿利克斯的耗竭扰乱了Vps 26和Vps 29的膜募集,并改变了空泡分选受体(VSR)的内体定位。总之,阿利克斯作为一个独特的retromer核心亚复合物调节器的功能,通过协调受体介导的可溶性蛋白质的液泡分选。
The endosomal sorting complex required for transport (ESCRT) machinery in multicellular organisms plays canonical functions in multivesicular body (MVB) biogenesis and membrane protein sorting. Nonetheless, its critical role in the sorting of soluble vacuolar proteins and its interplay with endosomal recycling machinery have yet to be reported. In this study, we demonstrate that Arabidopsis ESCRT-associated ALIXinteracts with the retromer core subunitsto regulate their recruitment onto endosome membrane for recycling of vacuolar sorting receptors (VSRs) for efficient sorting of soluble vacuolar proteins. This work provides molecular insights into the unique properties of ALIX in regulating vacuolar transport of soluble proteins, thus shedding new light on the crosstalk and coordination between the vacuolar trafficking and endosomal recycling pathways in plants. Vacuolar proteins play essential roles in plant physiology and development, but the factors and the machinery regulating their vesicle trafficking through the endomembrane compartments remain largely unknown. We and others have recently identified an evolutionarily conserved plant endosomal sorting complex required for transport (ESCRT)-associated protein apoptosis-linked gene-2 interacting protein X (ALIX), which plays canonical functions in the biogenesis of the multivesicular body/prevacuolar compartment (MVB/PVC) and in the sorting of ubiquitinated membrane proteins. In this study, we elucidate the roles and underlying mechanism of ALIX in regulating vacuolar transport of soluble proteins, beyond its conventional ESCRT function in eukaryotic cells. We show that ALIX colocalizes and physically interacts with the retromer core subunits Vps26 and Vps29 in planta. Moreover, double-mutant analysis reveals the genetic interaction of ALIX with Vps26 and Vps29 for regulating trafficking of soluble vacuolar proteins. Interestingly, depletion of ALIX perturbs membrane recruitment of Vps26 and Vps29 and alters the endosomal localization of vacuolar sorting receptors (VSRs). Taken together, ALIX functions as a unique retromer core subcomplex regulator by orchestrating receptor-mediated vacuolar sorting of soluble proteins.
DOI: 10.1016/j.str.2009.04.007
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