Journal article
TRPC3 signalling contributes to the biogenesis of extracellular vesicles
- Abstract:
- 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 Ca2+-permeable transient receptor potential (TRP) channel TRPC3 in EV-mediated communication. We found that specific activation of TRPC3 increased Ca2+ signalling in SKOV3 cells and stimulated an immediate increase in EV release. Ca2+-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 Ca2+-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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.3MB, Terms of use)
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- Publisher copy:
- 10.1002/jex2.132
Authors
+ Biotechnology and Biological Sciences Research Council
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- Funder identifier:
- https://ror.org/00cwqg982
- Publisher:
- Wiley
- Journal:
- Journal of Extracellular Biology More from this journal
- Volume:
- 3
- Issue:
- 1
- Article number:
- e132
- Place of publication:
- United States
- Publication date:
- 2023-12-25
- Acceptance date:
- 2023-12-08
- DOI:
- EISSN:
-
2768-2811
- ISSN:
-
2768-2811
- Pmid:
-
38938673
- Language:
-
English
- Keywords:
- Pubs id:
-
1635098
- Local pid:
-
pubs:1635098
- Deposit date:
-
2025-01-07
- ARK identifier:
Terms of use
- Copyright holder:
- Padbury et al
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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