Rhotekin-1 is a novel interacting protein and regulator of TRPC6 activity.

Boris Lavanderos, Octavio Orellana-Serradell, Diego Maureira, Pablo Cruz, Ian Silva, Jorge Toledo, Mariela González-Avendaño, Joaquín López, Rodrigo Santos, Felipe Arancibia, Diego Varela, Mónica Cáceres, Ariela Vergara-Jaque, Oscar Cerda
{"title":"Rhotekin-1 is a novel interacting protein and regulator of TRPC6 activity.","authors":"Boris Lavanderos, Octavio Orellana-Serradell, Diego Maureira, Pablo Cruz, Ian Silva, Jorge Toledo, Mariela González-Avendaño, Joaquín López, Rodrigo Santos, Felipe Arancibia, Diego Varela, Mónica Cáceres, Ariela Vergara-Jaque, Oscar Cerda","doi":"10.1111/febs.70028","DOIUrl":null,"url":null,"abstract":"<p><p>Dysregulation of Transient Receptor Potential Canonical 6 (TRPC6) channel is associated with pathologies in which cell contraction is relevant. Therefore, understanding the molecular mechanisms underlying the regulation of actin cytoskeletal function by TRPC6 is important. Here, we observed that TRPC6 upregulates the activity of RhoA GTPase, affecting the organization and polymerization of the actin cytoskeleton and focal adhesion dynamics. Moreover, TRPC6 activity promoted cell contraction and migration. Using mass spectrometry, we identified Rhotekin-1 (RTKN-1), an effector of RhoA, as a new TRPC6-interacting protein. In addition, RTKN-1 expression prevented the effects of TRPC6 on cell contraction, migration, and spreading. Moreover, calcium imaging, TRPC6-jGCaMP8f recordings, and patch clamp assays showed that RTKN-1 acts as a negative regulator of TRPC6 activity by reducing the abundance of TRPC6 in the plasma membrane through a mechanism that depends on RhoA activation. In this context, we found that RTKN-1 expression increased the endocytosis of TRPC6 in the early endosome compartment. In summary, these results suggest RTKN-1 as a new interactor and regulator of TRPC6 activity through a novel mechanism involving the modulation of TRPC6 trafficking.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FEBS journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/febs.70028","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Dysregulation of Transient Receptor Potential Canonical 6 (TRPC6) channel is associated with pathologies in which cell contraction is relevant. Therefore, understanding the molecular mechanisms underlying the regulation of actin cytoskeletal function by TRPC6 is important. Here, we observed that TRPC6 upregulates the activity of RhoA GTPase, affecting the organization and polymerization of the actin cytoskeleton and focal adhesion dynamics. Moreover, TRPC6 activity promoted cell contraction and migration. Using mass spectrometry, we identified Rhotekin-1 (RTKN-1), an effector of RhoA, as a new TRPC6-interacting protein. In addition, RTKN-1 expression prevented the effects of TRPC6 on cell contraction, migration, and spreading. Moreover, calcium imaging, TRPC6-jGCaMP8f recordings, and patch clamp assays showed that RTKN-1 acts as a negative regulator of TRPC6 activity by reducing the abundance of TRPC6 in the plasma membrane through a mechanism that depends on RhoA activation. In this context, we found that RTKN-1 expression increased the endocytosis of TRPC6 in the early endosome compartment. In summary, these results suggest RTKN-1 as a new interactor and regulator of TRPC6 activity through a novel mechanism involving the modulation of TRPC6 trafficking.

Rhotekin-1是一种新型相互作用蛋白,也是TRPC6活性的调节因子。
瞬时受体电位规范6 (TRPC6)通道的失调与细胞收缩相关的病理有关。因此,了解TRPC6调控肌动蛋白细胞骨架功能的分子机制是很重要的。在这里,我们观察到TRPC6上调RhoA GTPase的活性,影响肌动蛋白细胞骨架的组织和聚合以及局灶粘附动力学。此外,TRPC6活性促进细胞收缩和迁移。通过质谱分析,我们鉴定出RhoA的效应蛋白Rhotekin-1 (RTKN-1)是一种新的trpc6相互作用蛋白。此外,RTKN-1的表达阻止了TRPC6对细胞收缩、迁移和扩散的影响。此外,钙成像、TRPC6- jgcamp8f记录和膜片钳实验表明,rtkn1通过依赖于RhoA激活的机制,通过降低质膜中TRPC6的丰度,作为TRPC6活性的负调节因子。在这种情况下,我们发现RTKN-1的表达增加了早期核内体室中TRPC6的内吞作用。综上所述,这些结果表明RTKN-1是一种新的相互作用因子和TRPC6活性调节剂,通过一种涉及TRPC6转运调节的新机制。
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
自引率
0.00%
发文量
0
×
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