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固定化学计量的TRPC1-TRPC5串联体对G蛋白的独特反应。

Unique responses of the fixed stoichiometric TRPC1-TRPC5 concatemer to G proteins.

作者信息

Kang Hana, So Insuk

机构信息

Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.

出版信息

Front Physiol. 2024 Sep 27;15:1392980. doi: 10.3389/fphys.2024.1392980. eCollection 2024.

DOI:10.3389/fphys.2024.1392980
PMID:39397856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11466768/
Abstract

Transient receptor potential canonical (TRPC)5 channel is a non-selective cation channel that plays a significant role in membrane depolarization and calcium influx. TRPC5 not only forms homotetramers itself but also heterotetramers with TRPC1. However, accurately testing and confirming these heterotetrameric channels at specific ratios has proven challenging. Therefore, creating heteromeric concatemers of TRPC5 and TRPC1 with a fixed stoichiometry of 1:1 becomes essential. This study aims to meticulously identify and reaffirm the properties of TRPC5 homomers and heteromers with a 1:1 fixed stoichiometry to determine the optimal ratio for the TRPC1/5 heterotetramer. The overall characteristics were consistent with those of the previous studies, but several specific features were different. The TRPC1-TRPC5 concatemer is activated by Englerin A and GQL, whereas carbachol alone does not trigger its activation. Additionally, GQL significantly inhibited the current when co-expressed with the concatemer. Interestingly, carbachol can activate the TRPC1-TRPC5 concatemer in the presence of internal GTPγS, highlighting the influence of intracellular signaling conditions on its activation. Meanwhile, the TRPC5-TRPC5 concatemer is responsive to both carbachol and Englerin A. In conclusion, we provide evidence that the TRPC1-TRPC5 heteromeric concatemer with fixed stoichiometry need specific conditions to respond to carbachol, whereas the TRPC5-TRPC5 homomeric concatemer responds physiologically to carbachol. Additional research may be necessary to ascertain the optimal stoichiometry for the TRPC1-TRPC5 concatemer to enhance its electrophysiological properties.

摘要

瞬时受体电位香草酸亚型5(TRPC)5通道是一种非选择性阳离子通道,在膜去极化和钙内流中起重要作用。TRPC5不仅自身形成同源四聚体,还与TRPC1形成异源四聚体。然而,准确检测和确认这些特定比例的异源四聚体通道已被证明具有挑战性。因此,创建具有1:1固定化学计量比的TRPC5和TRPC1异源连接体变得至关重要。本研究旨在精心鉴定和再次确认具有1:1固定化学计量比的TRPC5同源体和异源体的特性,以确定TRPC1/5异源四聚体的最佳比例。总体特征与先前研究一致,但有几个特定特征有所不同。TRPC1-TRPC5连接体被恩格勒菌素A和GQL激活,而单独的卡巴胆碱不会触发其激活。此外,GQL与连接体共表达时会显著抑制电流。有趣的是,在细胞内存在GTPγS的情况下,卡巴胆碱可以激活TRPC1-TRPC5连接体,突出了细胞内信号传导条件对其激活的影响。同时,TRPC5-TRPC5连接体对卡巴胆碱和恩格勒菌素A均有反应。总之,我们提供的证据表明,具有固定化学计量比的TRPC1-TRPC5异源连接体需要特定条件才能对卡巴胆碱作出反应,而TRPC5-TRPC5同源连接体对卡巴胆碱有生理反应。可能需要进一步研究以确定TRPC1-TRPC5连接体的最佳化学计量比,以增强其电生理特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/7b9d3a46fe74/fphys-15-1392980-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/e7966823ece9/fphys-15-1392980-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/7e2532e9bc56/fphys-15-1392980-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/ae8a74fe1681/fphys-15-1392980-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/b2ed8baaf763/fphys-15-1392980-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/9af834ee86e0/fphys-15-1392980-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/ad5fb9728ed5/fphys-15-1392980-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/370d13261777/fphys-15-1392980-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/7b9d3a46fe74/fphys-15-1392980-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/e7966823ece9/fphys-15-1392980-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/7e2532e9bc56/fphys-15-1392980-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/ae8a74fe1681/fphys-15-1392980-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/b2ed8baaf763/fphys-15-1392980-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/9af834ee86e0/fphys-15-1392980-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/ad5fb9728ed5/fphys-15-1392980-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/370d13261777/fphys-15-1392980-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d17/11466768/7b9d3a46fe74/fphys-15-1392980-g008.jpg

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Subunit composition, molecular environment, and activation of native TRPC channels encoded by their interactomes.由其相互作用组编码的天然瞬时受体电位阳离子通道(TRPC通道)的亚基组成、分子环境及激活
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Lower troponin expression in the right ventricle of rats explains interventricular differences in E-C coupling.大鼠右心室心尖球蛋白表达降低解释了室间电耦合的差异。
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