Functional Large-Conductance Calcium and Voltage-Gated Potassium Channels in Extracellular Vesicles Act As Gatekeepers of Structural and Functional Integrity

Shridhar Sanghvi; Divya Sridharan; Parker Evans; Julie Dougherty; Kalina Szteyn; Denis Gabrilovich; Mayukha Dyta; Jessica Weist; Sandrine V Pierre; Shubha Gururaja Rao; Dan R Halm; Tingting Chen; Panagiotis S Athanasopoulos; Amalia M Dolga; Lianbo Yu; Mahmood Khan; Harpreet Singh

doi:10.1038/s41467-024-55379-4

Functional Large-Conductance Calcium and Voltage-Gated Potassium Channels in Extracellular Vesicles Act As Gatekeepers of Structural and Functional Integrity

Shridhar Sanghvi, Divya Sridharan, Parker Evans, Julie Dougherty, Kalina Szteyn, Denis Gabrilovich, Mayukha Dyta, Jessica Weist, Sandrine V Pierre, Shubha Gururaja Rao, Dan R Halm, Tingting Chen, Panagiotis S Athanasopoulos, Amalia M Dolga, Lianbo Yu, Mahmood Khan, Harpreet Singh

Neuroscience, Cell Biology, and Physiology (NCBP)

Research output: Contribution to journal › Article › peer-review

Abstract

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 (BK Ca) in the membrane of EVs. Furthermore, we establish that BK Ca is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BK Ca in functioning as gatekeepers and maintaining EV-mediated signaling.

Original language	English
Pages (from-to)	42
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-55379-4
State	Published - Jan 2 2025

Keywords

Extracellular Vesicles/metabolism
Humans
HEK293 Cells
Large-Conductance Calcium-Activated Potassium Channels/metabolism
Animals
Calcium/metabolism
Potassium Channels, Voltage-Gated/metabolism
Signal Transduction
Mice
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism

Disciplines

Neuroscience and Neurobiology

Access to Document

10.1038/s41467-024-55379-4

s41467-024-55379-4Final published version, 3.11 MBLicense: CC BY

Cite this

Sanghvi, S., Sridharan, D., Evans, P., Dougherty, J., Szteyn, K., Gabrilovich, D., Dyta, M., Weist, J., Pierre, S. V., Gururaja Rao, S., Halm, D. R., Chen, T., Athanasopoulos, P. S., Dolga, A. M., Yu, L., Khan, M., & Singh, H. (2025). Functional Large-Conductance Calcium and Voltage-Gated Potassium Channels in Extracellular Vesicles Act As Gatekeepers of Structural and Functional Integrity. Nature Communications, 16(1), 42. https://doi.org/10.1038/s41467-024-55379-4

Sanghvi, S, Sridharan, D, Evans, P, Dougherty, J, Szteyn, K, Gabrilovich, D, Dyta, M, Weist, J, Pierre, SV, Gururaja Rao, S, Halm, DR, Chen, T, Athanasopoulos, PS, Dolga, AM, Yu, L, Khan, M & Singh, H 2025, 'Functional Large-Conductance Calcium and Voltage-Gated Potassium Channels in Extracellular Vesicles Act As Gatekeepers of Structural and Functional Integrity', Nature Communications, vol. 16, no. 1, pp. 42. https://doi.org/10.1038/s41467-024-55379-4

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abstract = "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 (BK Ca) in the membrane of EVs. Furthermore, we establish that BK Ca is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BK Ca in functioning as gatekeepers and maintaining EV-mediated signaling. ",

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AU - Halm, Dan R

AU - Chen, Tingting

AU - Athanasopoulos, Panagiotis S

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