TRPC3 signalling contributes to the biogenesis of extracellular vesicles.

Autor: Padbury EH; Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK.; Kavli Institute for Nanoscience Discovery University of Oxford Oxford UK., Bálint Š; Kennedy Institute of Rheumatology University of Oxford Oxford UK., Carollo E; Department of Biological and Medical Sciences Oxford Brookes University Oxford UK., Carter DRF; Department of Biological and Medical Sciences Oxford Brookes University Oxford UK.; Evox Therapeutics Limited Oxford UK., Becker EBE; Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK.; Kavli Institute for Nanoscience Discovery University of Oxford Oxford UK.
Jazyk: angličtina
Zdroj: Journal of extracellular biology [J Extracell Biol] 2023 Dec 25; Vol. 3 (1), pp. e132. Date of Electronic Publication: 2023 Dec 25 (Print Publication: 2024).
DOI: 10.1002/jex2.132
Abstrakt: Extracellular vesicles (EVs) contribute to a wide range of pathological processes including cancer progression, yet the molecular mechanisms underlying their biogenesis remain incompletely characterized. The development of tetraspanin-based pHluorin reporters has enabled the real-time analysis of EV release at the plasma membrane. Here, we employed CD81-pHluorin to investigate mechanisms of EV release in ovarian cancer (OC) cells and report a novel role for the Ca 2+ -permeable transient receptor potential (TRP) channel TRPC3 in EV-mediated communication. We found that specific activation of TRPC3 increased Ca 2+ signalling in SKOV3 cells and stimulated an immediate increase in EV release. Ca 2+ -stimulants histamine and ionomycin likewise induced EV release, and imaging analysis revealed distinct stimulation-dependent temporal and spatial release dynamics. Interestingly, inhibition of TRPC3 attenuated histamine-stimulated Ca 2+ -entry and EV release, indicating that TRPC3 is likely to act downstream of histamine signalling in EV biogenesis. Furthermore, we found that direct activation of TRPC3 as well as the application of EVs derived from TRPC3-activated cells increased SKOV3 proliferation. Our data provides insights into the molecular mechanisms and dynamics underlying EV release in OC cells, proposing a key role for TRPC3 in EV biogenesis.
Competing Interests: The authors report no conflict of interest.
(© 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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