Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2024-12-23 DOI:10.1002/1873-3468.15084

Yugo Miyata, Megumi Nishimura, Aya Nagata, Xu Jing, Cheryl S. Sultan, Risa Kuribayashi, Katsuya Takahashi, Yongchan Lee, Tomohiro Nishizawa, Katsumori Segawa

{"title":"Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family","authors":"Yugo Miyata, Megumi Nishimura, Aya Nagata, Xu Jing, Cheryl S. Sultan, Risa Kuribayashi, Katsuya Takahashi, Yongchan Lee, Tomohiro Nishizawa, Katsumori Segawa","doi":"10.1002/1873-3468.15084","DOIUrl":null,"url":null,"abstract":"<p>Phospholipids are asymmetrically distributed in the plasma membrane (PM), and scramblases disrupt this asymmetry by shuffling phospholipids. We recently identified mouse Tmem63b as a membrane structure-responsive scramblase. Tmem63b belongs to the TMEM63/OSCA family of ion channels; however, the conservation of the scramblase activity within this family remains unclear. We expressed human TMEM63 paralogs, TMEM63B orthologs, and plant OSCA1.1 in <i>Tmem63b</i>-deficient mouse pro-B cells and found that vertebrate TMEM63B orthologs exhibit scramblase activity at the PM. Previously, ten pathogenic human TMEM63B variants were identified, some of which exhibited constitutive scramblase activity. Upon expressing all variants, we found that nine variants displayed constitutive scramblase activity. These results suggest that membrane structure-responsive scramblase activity at the PM is conserved among vertebrate TMEM63B orthologs.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 5","pages":"656-666"},"PeriodicalIF":3.5000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/1873-3468.15084","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}

引用次数: 0

Abstract

Phospholipids are asymmetrically distributed in the plasma membrane (PM), and scramblases disrupt this asymmetry by shuffling phospholipids. We recently identified mouse Tmem63b as a membrane structure-responsive scramblase. Tmem63b belongs to the TMEM63/OSCA family of ion channels; however, the conservation of the scramblase activity within this family remains unclear. We expressed human TMEM63 paralogs, TMEM63B orthologs, and plant OSCA1.1 in Tmem63b-deficient mouse pro-B cells and found that vertebrate TMEM63B orthologs exhibit scramblase activity at the PM. Previously, ten pathogenic human TMEM63B variants were identified, some of which exhibited constitutive scramblase activity. Upon expressing all variants, we found that nine variants displayed constitutive scramblase activity. These results suggest that membrane structure-responsive scramblase activity at the PM is conserved among vertebrate TMEM63B orthologs.

Abstract Image

查看原文本刊更多论文

TMEM63/OSCA家族的膜结构响应脂质超燃酶活性。

磷脂在质膜（PM）中不对称分布，而超燃酶通过重组磷脂来破坏这种不对称。我们最近发现小鼠Tmem63b是一种响应膜结构的超燃酶。Tmem63b属于TMEM63/OSCA离子通道家族；然而，该家族中超燃酶活性的保存情况仍不清楚。我们在缺乏TMEM63B的小鼠前b细胞中表达了人类TMEM63同源物、TMEM63B同源物和植物OSCA1.1，发现脊椎动物TMEM63B同源物在PM处表现出促裂酶活性。此前，已鉴定出10种致病性人类TMEM63B变异，其中一些表现出构成型扰变酶活性。在表达所有变异体后，我们发现9个变异体显示了组成型扰变酶活性。这些结果表明，在脊椎动物TMEM63B同源物中，膜结构响应的超扰酶活性在PM处是保守的。

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

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.