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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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Publisher copy:
10.1002/jex2.132

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0001-8258-7113
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Oxford college:
Wadham College
Role:
Author
ORCID:
0000-0002-5238-4902



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:

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