ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-05-14 DOI:10.1016/j.jbc.2025.110236

TianTian Lu,Saori Umeshita,Kae Imanishi,Yicheng Wang,Yi-Shi Liu,Masamichi Nagae,Yuya Senoo,Kazutaka Ikeda,Morihisa Fujita,Taroh Kinoshita,Yoshiko Murakami

{"title":"ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis.","authors":"TianTian Lu,Saori Umeshita,Kae Imanishi,Yicheng Wang,Yi-Shi Liu,Masamichi Nagae,Yuya Senoo,Kazutaka Ikeda,Morihisa Fujita,Taroh Kinoshita,Yoshiko Murakami","doi":"10.1016/j.jbc.2025.110236","DOIUrl":null,"url":null,"abstract":"Glycosylphosphatidylinositol (GPI) serves as a membrane anchor of numerous cell surface proteins. It is synthesized in the endoplasmic reticulum from phosphatidylinositol (PI) by stepwise reactions and transferred to the C-terminus of the protein. Defects in genes involved in GPI biosynthesis affect the expression of GPI-anchored proteins (GPI-APs) or their structure, causing the neurological disorder, inherited GPI deficiency (IGD). Individuals with ARV1 deficiency have symptoms resembling IGD, but how ARV1 regulates GPI biosynthesis is poorly understood. Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function. ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay. Collectively, our results suggest that ARV1 facilitates efficient recruitment of PI to GPI-GnT, thereby playing a critical role in the regulation of GPI-AP expression.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"42 1","pages":"110236"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jbc.2025.110236","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Glycosylphosphatidylinositol (GPI) serves as a membrane anchor of numerous cell surface proteins. It is synthesized in the endoplasmic reticulum from phosphatidylinositol (PI) by stepwise reactions and transferred to the C-terminus of the protein. Defects in genes involved in GPI biosynthesis affect the expression of GPI-anchored proteins (GPI-APs) or their structure, causing the neurological disorder, inherited GPI deficiency (IGD). Individuals with ARV1 deficiency have symptoms resembling IGD, but how ARV1 regulates GPI biosynthesis is poorly understood. Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function. ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay. Collectively, our results suggest that ARV1 facilitates efficient recruitment of PI to GPI-GnT, thereby playing a critical role in the regulation of GPI-AP expression.

查看原文本刊更多论文

ARV1是启动糖基磷脂酰肌醇生物合成酶的一个组分。

糖基磷脂酰肌醇（GPI）是许多细胞表面蛋白的膜锚。它是由磷脂酰肌醇（PI）在内质网中通过分步反应合成并转移到蛋白质的c端。参与GPI生物合成的基因缺陷影响GPI锚定蛋白（GPI- aps）的表达或其结构，导致遗传性GPI缺乏症（IGD）。ARV1缺乏的个体有类似IGD的症状，但ARV1如何调节GPI的生物合成尚不清楚。在这里，我们发现ARV1作为启动GPI生物合成酶的一个组成部分，GPI n -乙酰氨基葡萄糖转移酶（GPI- gnt）复合物，形成一个环结构，正如AlphaFold3所预测的那样。ARV1与PIGQ（一种GPI-GnT成分）相关，ARV1突变体在这种关联中存在缺陷，失去了增强GPI-GnT活性的能力，这表明与PIGQ的关联对ARV1的功能至关重要。在体外酶分析中，含arv1的GPI-GnT比不含arv1的GPI-GnT更有效地利用PI。总之，我们的研究结果表明，ARV1促进了PI向GPI-GnT的有效募集，从而在GPI-AP表达的调控中发挥了关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

期刊介绍： The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.