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

Hana Kang; Insuk So

doi:10.3389/fphys.2024.1392980

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

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

Authors

Hana Kang¹, Insuk So^{1

2}

Affiliations

¹ Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
² Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.

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 G_iQL, whereas carbachol alone does not trigger its activation. Additionally, G_qQL 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.

Keywords: Englerin A; G protein; GTPγS; TRPC1; TRPC5; concatemer; heteromer; homomer.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by National Research Foundation of Korea grant 2020R1A2C1012670 and 2021R1A4A2001857 (IS), Seoul National University Hospital Research Fund 04-2020-0220 (IS), Education and Research Encouragement Fund of Seoul National University Hospital (IS), BK21 FOUR education program scholarship (HK).