{"title":"TMEM63/OSCA家族的膜结构响应脂质超燃酶活性。","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":"{\"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}","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}
Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family
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.
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.
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