Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55379-4 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shridhar Sanghvi |
| collection | DOAJ |
| description | 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 (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. |
| format | Article |
| id | doaj-art-d34be5ba3a0540a7bb5dbf331397d7ba |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d34be5ba3a0540a7bb5dbf331397d7ba2025-01-05T12:38:21ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-024-55379-4Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrityShridhar Sanghvi0Divya Sridharan1Parker Evans2Julie Dougherty3Kalina Szteyn4Denis Gabrilovich5Mayukha Dyta6Jessica Weist7Sandrine V. Pierre8Shubha Gururaja Rao9Dan R. Halm10Tingting Chen11Panagiotis S. Athanasopoulos12Amalia M. Dolga13Lianbo Yu14Mahmood Khan15Harpreet Singh16Department of Molecular Cellular and Developmental Biology, The Ohio State UniversityDivision of Basic and Translation Research, Department of Emergency Medicine, The Ohio State University Wexner Medical CenterDepartment of Mechanical and Aerospace Engineering, The Ohio State UniversityDivision of Basic and Translation Research, Department of Emergency Medicine, The Ohio State University Wexner Medical CenterDepartment of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterDepartment of Molecular Cellular and Developmental Biology, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterDivision of Basic and Translation Research, Department of Emergency Medicine, The Ohio State University Wexner Medical CenterDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall UniversityDepartment of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern UniversityDepartment of Neuroscience, Cell Biology, and Physiology, Wright State UniversityDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of GroningenDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of GroningenDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of GroningenDepartment of Biomedical Informatics, The Ohio State UniversityDivision of Basic and Translation Research, Department of Emergency Medicine, The Ohio State University Wexner Medical CenterDepartment of Molecular Cellular and Developmental Biology, The Ohio State UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55379-4 |
| spellingShingle | 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 Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity Nature Communications |
| title | Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| title_full | Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| title_fullStr | Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| title_full_unstemmed | Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| title_short | Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| title_sort | functional large conductance calcium and voltage gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity |
| url | https://doi.org/10.1038/s41467-024-55379-4 |
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