Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Graziana Modica, Laura Tejeda-Valencia, Etienne Sauvageau, Seda Yasa, Juliette Maes, Olga Skorobogata, Stephane Lefrancois
{"title":"Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.","authors":"Graziana Modica, Laura Tejeda-Valencia, Etienne Sauvageau, Seda Yasa, Juliette Maes, Olga Skorobogata, Stephane Lefrancois","doi":"10.1242/jcs.262177","DOIUrl":null,"url":null,"abstract":"<p><p>Rab7A has a key role in regulating membrane trafficking at late endosomes. By interacting with several different effectors, this small GTPase controls late endosome mobility, orchestrates fusion events between late endosomes and lysosomes, and participates in the formation of and regulates the fusion between autophagosomes and lysosomes. Rab7A is also responsible for the spatiotemporal recruitment of retromer, which is required for the endosome-to-TGN retrieval of cargo-receptors such as sortilin and CI-MPR. Recently several post-translational modifications have been shown to modulate Rab7A functions, including palmitoylation, ubiquitination and phosphorylation. Here we show that phosphorylation of Rab7A at serine 72 is important to modulate its interaction with retromer, as the non-phosphorylatable Rab7AS72A mutant is not able to interact with and recruit retromer to late endosomes. We have previously shown that Rab7A palmitoylation is also required for efficient retromer recruitment. We found that palmitoylation of Rab7AS72A is reduced compared to the wild-type protein, suggesting an interplay between S72 phosphorylation and palmitoylation in regulating the Rab7A/retromer interaction. Finally, we identify NEK7 as a kinase required to phosphorylate Rab7A to promote retromer binding and recruitment.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cell science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/jcs.262177","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Rab7A has a key role in regulating membrane trafficking at late endosomes. By interacting with several different effectors, this small GTPase controls late endosome mobility, orchestrates fusion events between late endosomes and lysosomes, and participates in the formation of and regulates the fusion between autophagosomes and lysosomes. Rab7A is also responsible for the spatiotemporal recruitment of retromer, which is required for the endosome-to-TGN retrieval of cargo-receptors such as sortilin and CI-MPR. Recently several post-translational modifications have been shown to modulate Rab7A functions, including palmitoylation, ubiquitination and phosphorylation. Here we show that phosphorylation of Rab7A at serine 72 is important to modulate its interaction with retromer, as the non-phosphorylatable Rab7AS72A mutant is not able to interact with and recruit retromer to late endosomes. We have previously shown that Rab7A palmitoylation is also required for efficient retromer recruitment. We found that palmitoylation of Rab7AS72A is reduced compared to the wild-type protein, suggesting an interplay between S72 phosphorylation and palmitoylation in regulating the Rab7A/retromer interaction. Finally, we identify NEK7 as a kinase required to phosphorylate Rab7A to promote retromer binding and recruitment.

丝氨酸 72 上的磷酸化调节 Rab7A 棕榈酰化和 retromer 招募。
Rab7A 在调节晚期内体的膜贩运方面起着关键作用。通过与几种不同的效应物相互作用,这种小 GTPase 可控制晚期内体的流动性,协调晚期内体与溶酶体之间的融合事件,并参与形成和调节自噬体与溶酶体之间的融合。Rab7A 还负责 retromer 的时空招募,而 retromer 是内质体到 TGN 检索货物受体(如 sortilin 和 CI-MPR)所必需的。最近有研究表明,几种翻译后修饰可调节 Rab7A 的功能,包括棕榈酰化、泛素化和磷酸化。我们在这里发现,Rab7A 在丝氨酸 72 处的磷酸化对调节其与 retromer 的相互作用非常重要,因为不可磷酸化的 Rab7AS72A 突变体无法与 retromer 相互作用并将其招募到晚期内体。我们之前已经证明,Rab7A棕榈酰化也是有效招募 retromer 的必要条件。我们发现,与野生型蛋白相比,Rab7AS72A 的棕榈酰化减少了,这表明 S72 磷酸化和棕榈酰化在调节 Rab7A 与 retromer 的相互作用中相互作用。最后,我们确定 NEK7 是使 Rab7A 磷酸化以促进 retromer 结合和招募所需的激酶。
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
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
×
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:481959085
Book学术官方微信