Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging
Abstract Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca2+ channel, plays a crucial role in intracellular Ca2+ homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca2+ influx at plasma membrane microdomains...
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oai:doaj.org-article:2322ff8a64f345bcba792187b56ee6892021-12-02T17:19:16ZDistinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging10.1038/s41598-021-97326-z2045-2322https://doaj.org/article/2322ff8a64f345bcba792187b56ee6892021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97326-zhttps://doaj.org/toc/2045-2322Abstract Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca2+ channel, plays a crucial role in intracellular Ca2+ homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca2+ influx at plasma membrane microdomains. Using two different types of Ca2+ biosensors (Lyn-D3cpv and Kras-D3cpv) based on fluorescence resonance energy transfer, we investigate how Ca2+ influx generated by the TRPM7-specific agonist naltriben is mediated at the detergent-resistant membrane (DRM) and non-DRM regions. This study reveals that TRPM7-induced Ca2+ influx mainly occurs at the DRM, and chemically induced mechanical perturbations in the cell mechanosensitive apparatus substantially reduce Ca2+ influx through TRPM7, preferably located at the DRM. Such perturbations include the disintegration of lipid rafts, microtubules, or actomyosin filaments; the alteration of actomyosin contractility; and the inhibition of focal adhesion and Src kinases. These results suggest that the mechanical membrane environment contributes to the TRPM7 function and activity. Thus, this study provides a fundamental understanding of how the mechanical aspects of the cell membrane regulate the function of mechanosensitive channels.Irina StarostinaYoon-Kwan JangHeon-Su KimJung-Soo SuhSang-Hyun AhnGyu-Ho ChoiMyungeun SukTae-Jin KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Irina Starostina Yoon-Kwan Jang Heon-Su Kim Jung-Soo Suh Sang-Hyun Ahn Gyu-Ho Choi Myungeun Suk Tae-Jin Kim Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
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Abstract Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca2+ channel, plays a crucial role in intracellular Ca2+ homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca2+ influx at plasma membrane microdomains. Using two different types of Ca2+ biosensors (Lyn-D3cpv and Kras-D3cpv) based on fluorescence resonance energy transfer, we investigate how Ca2+ influx generated by the TRPM7-specific agonist naltriben is mediated at the detergent-resistant membrane (DRM) and non-DRM regions. This study reveals that TRPM7-induced Ca2+ influx mainly occurs at the DRM, and chemically induced mechanical perturbations in the cell mechanosensitive apparatus substantially reduce Ca2+ influx through TRPM7, preferably located at the DRM. Such perturbations include the disintegration of lipid rafts, microtubules, or actomyosin filaments; the alteration of actomyosin contractility; and the inhibition of focal adhesion and Src kinases. These results suggest that the mechanical membrane environment contributes to the TRPM7 function and activity. Thus, this study provides a fundamental understanding of how the mechanical aspects of the cell membrane regulate the function of mechanosensitive channels. |
format |
article |
author |
Irina Starostina Yoon-Kwan Jang Heon-Su Kim Jung-Soo Suh Sang-Hyun Ahn Gyu-Ho Choi Myungeun Suk Tae-Jin Kim |
author_facet |
Irina Starostina Yoon-Kwan Jang Heon-Su Kim Jung-Soo Suh Sang-Hyun Ahn Gyu-Ho Choi Myungeun Suk Tae-Jin Kim |
author_sort |
Irina Starostina |
title |
Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
title_short |
Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
title_full |
Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
title_fullStr |
Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
title_full_unstemmed |
Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging |
title_sort |
distinct calcium regulation of trpm7 mechanosensitive channels at plasma membrane microdomains visualized by fret-based single cell imaging |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/2322ff8a64f345bcba792187b56ee689 |
work_keys_str_mv |
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1718381015126245376 |