一个非典型的gprc5a信号通过核易位调节角质细胞的粘附和迁移。

IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sarah Chanteloube, Choua Ya, Gabrielle Le Provost, Aurore Berthier, Cindy Dieryckx, Sandrine Vadon-Le Goff, Florence Nadal, Bérengère Fromy, Romain Debret
{"title":"一个非典型的gprc5a信号通过核易位调节角质细胞的粘附和迁移。","authors":"Sarah Chanteloube,&nbsp;Choua Ya,&nbsp;Gabrielle Le Provost,&nbsp;Aurore Berthier,&nbsp;Cindy Dieryckx,&nbsp;Sandrine Vadon-Le Goff,&nbsp;Florence Nadal,&nbsp;Bérengère Fromy,&nbsp;Romain Debret","doi":"10.1096/fj.202400122R","DOIUrl":null,"url":null,"abstract":"<p>G-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) has been extensively studied in lung and various epithelial cancers. Nevertheless, its role in the skin remains to be elucidated. In this study, we sought to investigate the function of this receptor in skin biology. Our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed the reinduction of GPRC5A during wound healing at the leading edges in an ex vivo burn model, coinciding with the translocation of its C-terminal region into the nucleus. We identified the cleavage site of GPRC5A by N-TAILS analysis, and cathepsin G was characterized as the protease responsible for proteolysis in cultured cells. In order to gain a deeper understanding of the role of GPRC5A in keratinocytes, we performed a GPRC5A knockdown in N/TERT-1 cells using short-hairpin RNA. Our findings indicate a strong association between GPRC5A and adhesion regulation pathways. Additionally, our results demonstrate that GPRC5A<sup>KD</sup> enhances cell adhesion while reducing cell migration and differentiation. It is noteworthy that these effects were reversed by the addition of a recombinant polypeptide that mimics the C-terminal region of GPRC5A. In conclusion, our study reveals that GPRC5A plays an unexpected role in regulating keratinocyte behavior, with implications for its C-terminal region translocation into the nucleus. These results offer promising avenues for future research in the field of wound healing.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 2","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A noncanonical-GPRC5A signaling regulates keratinocyte adhesion and migration by nuclear translocation\",\"authors\":\"Sarah Chanteloube,&nbsp;Choua Ya,&nbsp;Gabrielle Le Provost,&nbsp;Aurore Berthier,&nbsp;Cindy Dieryckx,&nbsp;Sandrine Vadon-Le Goff,&nbsp;Florence Nadal,&nbsp;Bérengère Fromy,&nbsp;Romain Debret\",\"doi\":\"10.1096/fj.202400122R\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>G-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) has been extensively studied in lung and various epithelial cancers. Nevertheless, its role in the skin remains to be elucidated. In this study, we sought to investigate the function of this receptor in skin biology. Our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed the reinduction of GPRC5A during wound healing at the leading edges in an ex vivo burn model, coinciding with the translocation of its C-terminal region into the nucleus. We identified the cleavage site of GPRC5A by N-TAILS analysis, and cathepsin G was characterized as the protease responsible for proteolysis in cultured cells. In order to gain a deeper understanding of the role of GPRC5A in keratinocytes, we performed a GPRC5A knockdown in N/TERT-1 cells using short-hairpin RNA. Our findings indicate a strong association between GPRC5A and adhesion regulation pathways. Additionally, our results demonstrate that GPRC5A<sup>KD</sup> enhances cell adhesion while reducing cell migration and differentiation. It is noteworthy that these effects were reversed by the addition of a recombinant polypeptide that mimics the C-terminal region of GPRC5A. In conclusion, our study reveals that GPRC5A plays an unexpected role in regulating keratinocyte behavior, with implications for its C-terminal region translocation into the nucleus. These results offer promising avenues for future research in the field of wound healing.</p>\",\"PeriodicalId\":50455,\"journal\":{\"name\":\"The FASEB Journal\",\"volume\":\"39 2\",\"pages\":\"\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-01-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The FASEB Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1096/fj.202400122R\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1096/fj.202400122R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

g蛋白偶联受体(G-Protein Coupled Receptor, Class C, Group 5, Member A, GPRC5A)在肺癌和各种上皮性癌症中已被广泛研究。然而,它在皮肤中的作用仍有待阐明。在这项研究中,我们试图研究该受体在皮肤生物学中的功能。我们的研究表明,它的表达响应人原代角质形成细胞的机械底物变化。此外,我们在离体烧伤模型中观察到GPRC5A在伤口愈合过程中前缘的再诱导,其c端区域易位到细胞核中。我们通过N-TAILS分析确定了GPRC5A的裂解位点,并确定了组织蛋白酶G是在培养细胞中负责蛋白水解的蛋白酶。为了更深入地了解GPRC5A在角质形成细胞中的作用,我们使用短发夹RNA在N/TERT-1细胞中进行了GPRC5A敲低。我们的研究结果表明GPRC5A与粘附调节途径之间存在很强的相关性。此外,我们的研究结果表明,GPRC5AKD增强细胞粘附,同时减少细胞迁移和分化。值得注意的是,通过添加一种模拟GPRC5A c端区域的重组多肽,这些效应被逆转。总之,我们的研究揭示了GPRC5A在调节角质形成细胞的行为中发挥了意想不到的作用,其c端区域易位到细胞核中。这些结果为未来伤口愈合领域的研究提供了有希望的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A noncanonical-GPRC5A signaling regulates keratinocyte adhesion and migration by nuclear translocation

A noncanonical-GPRC5A signaling regulates keratinocyte adhesion and migration by nuclear translocation

G-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) has been extensively studied in lung and various epithelial cancers. Nevertheless, its role in the skin remains to be elucidated. In this study, we sought to investigate the function of this receptor in skin biology. Our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed the reinduction of GPRC5A during wound healing at the leading edges in an ex vivo burn model, coinciding with the translocation of its C-terminal region into the nucleus. We identified the cleavage site of GPRC5A by N-TAILS analysis, and cathepsin G was characterized as the protease responsible for proteolysis in cultured cells. In order to gain a deeper understanding of the role of GPRC5A in keratinocytes, we performed a GPRC5A knockdown in N/TERT-1 cells using short-hairpin RNA. Our findings indicate a strong association between GPRC5A and adhesion regulation pathways. Additionally, our results demonstrate that GPRC5AKD enhances cell adhesion while reducing cell migration and differentiation. It is noteworthy that these effects were reversed by the addition of a recombinant polypeptide that mimics the C-terminal region of GPRC5A. In conclusion, our study reveals that GPRC5A plays an unexpected role in regulating keratinocyte behavior, with implications for its C-terminal region translocation into the nucleus. These results offer promising avenues for future research in the field of wound healing.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
×
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