SLC4A11 Revisited: Isoforms, Expression, Functions, and Unresolved Questions.

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biomolecules Pub Date : 2025-06-16 DOI:10.3390/biom15060875
Polina Alekseevna Kovaleva, Elena Sergeevna Kotova, Elena Ivanovna Sharova, Liubov Olegovna Skorodumova
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引用次数: 0

Abstract

The SLC4A11 gene encodes a membrane transporter implicated in congenital hereditary endothelial dystrophy, Harboyan syndrome, and certain cancers. Despite its clinical importance, current data on SLC4A11 expression patterns, transcript variants, and functional roles remain inconsistent and sometimes contradictory. We have systematized existing data, identified areas of consensus, and highlighted discrepancies. This review addresses SLC4A11 transcript and isoform diversity and how this complexity influences both the interpretation of its tissue expression patterns (particularly in the corneal endothelium) and the investigation of its functional roles in health and disease. Our review also untangles the evolving understanding of SLC4A11 function, from its initial classification as a bicarbonate transporter to its established roles in NH3- and pH-regulated H+/OH- transport, lactate efflux, cellular stress responses, and adhesion. The review details how pathogenic mutations disrupt protein maturation, membrane localization, or transport activity, contributing to corneal fluid imbalance and disease. We also discuss the emerging role of SLC4A11 in cancer metabolism and the common metabolic features of dystrophic corneas and tumors. Methodological challenges are appraised, encouraging caution in interpretation and the need for isoform-specific studies. Overall, this review provides a comprehensive update on SLC4A11 biology and identifies key gaps for future research.

SLC4A11重访:异构体,表达,功能和未解决的问题。
SLC4A11基因编码一种膜转运蛋白,与先天性遗传性内皮营养不良、Harboyan综合征和某些癌症有关。尽管SLC4A11具有重要的临床意义,但目前关于SLC4A11表达模式、转录物变异和功能作用的数据仍然不一致,有时甚至相互矛盾。我们对现有数据进行了系统化,确定了达成共识的领域,并突出了差异。本文综述了SLC4A11转录本和同种异构体的多样性,以及这种复杂性如何影响其组织表达模式(特别是角膜内皮)的解释,以及其在健康和疾病中的功能作用的研究。我们的综述还解开了对SLC4A11功能的不断发展的理解,从它最初作为碳酸氢盐转运体的分类到它在NH3-和ph调节的H+/OH-转运、乳酸外排、细胞应激反应和粘附中的作用。这篇综述详细介绍了致病性突变如何破坏蛋白质成熟、膜定位或运输活性,从而导致角膜液体失衡和疾病。我们还讨论了SLC4A11在癌症代谢中的新作用以及营养不良角膜和肿瘤的共同代谢特征。评估了方法上的挑战,鼓励谨慎解释和对同种异构体特异性研究的需要。总之,这篇综述提供了SLC4A11生物学的全面更新,并确定了未来研究的关键空白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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