{"title":"钾转运体的生物生成:疾病相关突变的影响。","authors":"Morgan Kok, Jeffrey L Brodsky","doi":"10.1080/10409238.2024.2369986","DOIUrl":null,"url":null,"abstract":"<p><p>The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies. In this review, we discuss the structure, function, and activity of a group of potassium-chloride cotransporters, the KCCs, as well as the related sodium-potassium-chloride cotransporters, the NKCCs. Diseases associated with each of the four KCCs and two NKCCs are also discussed. Particular emphasis is placed on how these complex membrane proteins fold and mature in the endoplasmic reticulum, how non-native forms of the cotransporters are destroyed in the cell, and which cellular factors oversee their maturation and transport to the cell surface. When known, we also outline how the levels and activities of each cotransporter are regulated. Open questions in the field and avenues for future investigations are further outlined.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444911/pdf/","citationCount":"0","resultStr":"{\"title\":\"The biogenesis of potassium transporters: implications of disease-associated mutations.\",\"authors\":\"Morgan Kok, Jeffrey L Brodsky\",\"doi\":\"10.1080/10409238.2024.2369986\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies. In this review, we discuss the structure, function, and activity of a group of potassium-chloride cotransporters, the KCCs, as well as the related sodium-potassium-chloride cotransporters, the NKCCs. Diseases associated with each of the four KCCs and two NKCCs are also discussed. Particular emphasis is placed on how these complex membrane proteins fold and mature in the endoplasmic reticulum, how non-native forms of the cotransporters are destroyed in the cell, and which cellular factors oversee their maturation and transport to the cell surface. When known, we also outline how the levels and activities of each cotransporter are regulated. Open questions in the field and avenues for future investigations are further outlined.</p>\",\"PeriodicalId\":10794,\"journal\":{\"name\":\"Critical Reviews in Biochemistry and Molecular Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444911/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Biochemistry and Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/10409238.2024.2369986\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/10409238.2024.2369986","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The biogenesis of potassium transporters: implications of disease-associated mutations.
The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies. In this review, we discuss the structure, function, and activity of a group of potassium-chloride cotransporters, the KCCs, as well as the related sodium-potassium-chloride cotransporters, the NKCCs. Diseases associated with each of the four KCCs and two NKCCs are also discussed. Particular emphasis is placed on how these complex membrane proteins fold and mature in the endoplasmic reticulum, how non-native forms of the cotransporters are destroyed in the cell, and which cellular factors oversee their maturation and transport to the cell surface. When known, we also outline how the levels and activities of each cotransporter are regulated. Open questions in the field and avenues for future investigations are further outlined.
期刊介绍:
As the discipline of biochemistry and molecular biology have greatly advanced in the last quarter century, significant contributions have been made towards the advancement of general medicine, genetics, immunology, developmental biology, and biophysics. Investigators in a wide range of disciplines increasingly require an appreciation of the significance of current biochemical and molecular biology advances while, members of the biochemical and molecular biology community itself seek concise information on advances in areas remote from their own specialties.
Critical Reviews in Biochemistry and Molecular Biology believes that well-written review articles prove an effective device for the integration and meaningful comprehension of vast, often contradictory, literature. Review articles also provide an opportunity for creative scholarship by synthesizing known facts, fruitful hypotheses, and new concepts. Accordingly, Critical Reviews in Biochemistry and Molecular Biology publishes high-quality reviews that organize, evaluate, and present the current status of high-impact, current issues in the area of biochemistry and molecular biology.
Topics are selected on the advice of an advisory board of outstanding scientists, who also suggest authors of special competence. The topics chosen are sufficiently broad to interest a wide audience of readers, yet focused enough to be within the competence of a single author. Authors are chosen based on their activity in the field and their proven ability to produce a well-written publication.