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Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging

Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca(2+) channel, plays a crucial role in intracellular Ca(2+) homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca(2+) influx at plasma membrane microdomains. U...

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Detalles Bibliográficos
Autores principales: Starostina, Irina, Jang, Yoon-Kwan, Kim, Heon-Su, Suh, Jung-Soo, Ahn, Sang-Hyun, Choi, Gyu-Ho, Suk, Myungeun, Kim, Tae-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429465/
https://www.ncbi.nlm.nih.gov/pubmed/34504177
http://dx.doi.org/10.1038/s41598-021-97326-z
Descripción
Sumario:Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca(2+) channel, plays a crucial role in intracellular Ca(2+) homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca(2+) influx at plasma membrane microdomains. Using two different types of Ca(2+) biosensors (Lyn-D3cpv and Kras-D3cpv) based on fluorescence resonance energy transfer, we investigate how Ca(2+) 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 Ca(2+) influx mainly occurs at the DRM, and chemically induced mechanical perturbations in the cell mechanosensitive apparatus substantially reduce Ca(2+) 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.