Flotillins in membrane trafficking and physiopathology

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Stéphane Bodin, Hadeer Elhabashy, Ewan Macdonald, Dominic Winter, Cécile Gauthier-Rouvière
{"title":"Flotillins in membrane trafficking and physiopathology","authors":"Stéphane Bodin,&nbsp;Hadeer Elhabashy,&nbsp;Ewan Macdonald,&nbsp;Dominic Winter,&nbsp;Cécile Gauthier-Rouvière","doi":"10.1111/boc.202400134","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>Flotillin 1 and 2 are highly conserved and homologous members of the stomatin, prohibitin, flotillin, HflK/C (SPFH) family. These ubiquitous proteins assemble into hetero-oligomers at the cytoplasmic membrane in sphingolipid-enriched domains. Flotillins play crucial roles in various cellular processes, likely by concentrating sphingosine. They primarily act as scaffolding protein complexes within membrane microdomains (also called lipid rafts) and induce endocytosis and trafficking. Their diverse cargos in the upregulated flotillin–induced trafficking (UFIT) pathway, including tyrosine kinase receptors, adhesion molecules, and neurotransmitter receptors, link them to a wide range of cellular processes and diseases. Consequently, flotillin upregulation has been associated with various pathological conditions such as cancer, metabolic disorders, and neurodegenerative diseases. Flotillins may also be co-opted by pathogens to facilitate their entry and growth within host cells.</p>\n \n <p>In this review, we examined recent advancements in elucidating the structure and functions of the flotillin protein complex, including its implications in favoring the generation of sphingosine 1-phosphate, an essential bioactive lipid. We emphasized how the recent cryo-electron microscopy (cryo-EM) structure of a truncated cone-shaped cage composed of 22 copies of flotillin 1 and 2 subunits has enhanced our understanding of the flotillin complex organization within membrane microdomains and its role in membrane remodeling. We also explored how flotillin upregulation can perturb endosomal trafficking and contribute to various pathologies.</p>\n \n <p>A comprehensive understanding of flotillin oligomer organization and function is crucial to developing targeted therapies for diseases associated with flotillin overexpression.</p>\n </section>\n </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 1","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775717/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of the Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/boc.202400134","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Flotillin 1 and 2 are highly conserved and homologous members of the stomatin, prohibitin, flotillin, HflK/C (SPFH) family. These ubiquitous proteins assemble into hetero-oligomers at the cytoplasmic membrane in sphingolipid-enriched domains. Flotillins play crucial roles in various cellular processes, likely by concentrating sphingosine. They primarily act as scaffolding protein complexes within membrane microdomains (also called lipid rafts) and induce endocytosis and trafficking. Their diverse cargos in the upregulated flotillin–induced trafficking (UFIT) pathway, including tyrosine kinase receptors, adhesion molecules, and neurotransmitter receptors, link them to a wide range of cellular processes and diseases. Consequently, flotillin upregulation has been associated with various pathological conditions such as cancer, metabolic disorders, and neurodegenerative diseases. Flotillins may also be co-opted by pathogens to facilitate their entry and growth within host cells.

In this review, we examined recent advancements in elucidating the structure and functions of the flotillin protein complex, including its implications in favoring the generation of sphingosine 1-phosphate, an essential bioactive lipid. We emphasized how the recent cryo-electron microscopy (cryo-EM) structure of a truncated cone-shaped cage composed of 22 copies of flotillin 1 and 2 subunits has enhanced our understanding of the flotillin complex organization within membrane microdomains and its role in membrane remodeling. We also explored how flotillin upregulation can perturb endosomal trafficking and contribute to various pathologies.

A comprehensive understanding of flotillin oligomer organization and function is crucial to developing targeted therapies for diseases associated with flotillin overexpression.

Abstract Image

膜转运和生理病理中的漂浮现象。
Flotillin 1和2是stomatin, prohibitin, Flotillin, HflK/C (SPFH)家族中高度保守的同源成员。这些无处不在的蛋白质在鞘脂富集区域的细胞质膜上组装成异聚物。Flotillins在各种细胞过程中发挥着至关重要的作用,可能是通过集中鞘氨醇。它们主要作为膜微域(也称为脂筏)内的支架蛋白复合物并诱导内吞和运输。它们在上调的flotilin诱导运输(UFIT)途径中的不同货物,包括酪氨酸激酶受体、粘附分子和神经递质受体,将它们与广泛的细胞过程和疾病联系起来。因此,flotilin的上调与各种病理状况,如癌症、代谢紊乱和神经退行性疾病有关。漂浮物也可能被病原体吸收,以促进它们在宿主细胞内的进入和生长。在这篇综述中,我们研究了最近在阐明flotillin蛋白复合物的结构和功能方面的进展,包括它在促进生成鞘氨醇1-磷酸(一种必需的生物活性脂质)方面的意义。我们强调了最近由22个flotillin 1和2亚基拷贝组成的截锥形笼的冷冻电镜(cro - em)结构如何增强了我们对膜微域内flotillin复合物组织及其在膜重塑中的作用的理解。我们还探讨了flotilin上调如何扰乱内体运输并导致各种病理。全面了解flotillin寡聚物的组织和功能对于开发与flotillin过表达相关疾病的靶向治疗至关重要。
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
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信