Interaction between ESCRT-III proteins and the yeast SERINC homolog Tms1.

IF 3.3 3区 生物学 Genetics Pub Date : 2024-09-13 DOI:10.1093/genetics/iyae132
Ralf Kölling
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Abstract

The endosomal sorting complex required for transport (ESCRT)-III is involved in membrane remodeling and abscission during intraluminal vesicle (ILV) formation at endosomes. Our data now suggest that ESCRT-III function could be connected to lipid remodeling of the endosomal membrane. This notion is based on our finding that ESCRT-III proteins bind to the yeast serine incorporator (SERINC) homolog Tms1. Human SERINC3 and SERINC5 are HIV-1 restriction factors and have been shown to act as scramblases, flipping phospholipids between membrane leaflets. Due to the extraordinarily high sequence conservation between Tms1 and human SERINCs, it is likely that Tms1 is also a scramblase. While deletion of TMS1 had only a moderate effect on the sorting of multivesicular body (MVB) cargo proteins, the simultaneous deletion of a component of the Vps55/Vps68 complex led to a strong synergistic phenotype. This pronounced synergism suggests that Tms1 and Vps55/Vps68 perform a parallel function at endosomes. Vps55/Vps68 loosely resembles Tms1 in its overall structure. Thus, it is possible that Vps55/Vps68 is also a scramblase. Since both Vps55 and Tms1 physically interact with ESCRT-III proteins, we propose that the recruitment of a scramblase plays a crucial role in ESCRT-III-dependent membrane remodeling at endosomes.
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ESCRT-III 蛋白与酵母 SERINC 同源物 Tms1 之间的相互作用。
运输所需的内体分选复合体(ESCRT)-III 参与了内体形成腔内囊泡(ILV)过程中的膜重塑和脱落。我们现在的数据表明,ESCRT-III 的功能可能与内体膜的脂质重塑有关。这一观点的依据是我们发现 ESCRT-III 蛋白与酵母丝氨酸整合子(SERINC)同源物 Tms1 结合。人类 SERINC3 和 SERINC5 是 HIV-1 限制因子,已被证明可作为扰乱酶,在膜小叶之间翻转磷脂。由于 Tms1 与人类 SERINCs 之间的序列保守性极高,因此 Tms1 很可能也是一种扰乱酶。虽然 TMS1 的缺失对多囊体(MVB)货物蛋白的分拣只有适度的影响,但同时缺失 Vps55/Vps68 复合物的一个成分会导致强烈的协同表型。这种明显的协同作用表明,Tms1 和 Vps55/Vps68 在内质体中发挥着平行的功能。Vps55/Vps68 的整体结构与 Tms1 非常相似。因此,Vps55/Vps68 也可能是一种扰乱酶。由于 Vps55 和 Tms1 都与 ESCRT-III 蛋白发生物理相互作用,我们认为扰乱酶的招募在 ESCRT-III 依赖性内体膜重塑中起着关键作用。
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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