TY - JOUR
T1 - Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity
AU - Sanghvi, Shridhar
AU - Sridharan, Divya
AU - Evans, Parker
AU - Dougherty, Julie
AU - Szteyn, Kalina
AU - Gabrilovich, Denis
AU - Dyta, Mayukha
AU - Weist, Jessica
AU - Pierre, Sandrine V.
AU - Gururaja Rao, Shubha
AU - Halm, Dan R.
AU - Chen, Tingting
AU - Athanasopoulos, Panagiotis S.
AU - Dolga, Amalia M.
AU - Yu, Lianbo
AU - Khan, Mahmood
AU - Singh, Harpreet
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025/1/2
Y1 - 2025/1/2
N2 - Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content. EVs are known to possess ion channels and transporters in their membrane but neither the function nor the role of these channels in EVs is known. In this study, we discover a functional calcium-activated large-conductance potassium channel (BKCa) in the membrane of EVs. Furthermore, we establish that BKCa is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BKCa in functioning as gatekeepers and maintaining EV-mediated signaling.
AB - Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content. EVs are known to possess ion channels and transporters in their membrane but neither the function nor the role of these channels in EVs is known. In this study, we discover a functional calcium-activated large-conductance potassium channel (BKCa) in the membrane of EVs. Furthermore, we establish that BKCa is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BKCa in functioning as gatekeepers and maintaining EV-mediated signaling.
UR - http://www.scopus.com/inward/record.url?scp=85214033735&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-55379-4
DO - 10.1038/s41467-024-55379-4
M3 - Article
C2 - 39747826
AN - SCOPUS:85214033735
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 42
ER -