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Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity

Author

Listed:
  • Shridhar Sanghvi

    (The Ohio State University
    The Ohio State University Wexner Medical Center)

  • Divya Sridharan

    (The Ohio State University Wexner Medical Center)

  • Parker Evans

    (The Ohio State University)

  • Julie Dougherty

    (The Ohio State University Wexner Medical Center)

  • Kalina Szteyn

    (The Ohio State University Wexner Medical Center)

  • Denis Gabrilovich

    (The Ohio State University)

  • Mayukha Dyta

    (The Ohio State University Wexner Medical Center)

  • Jessica Weist

    (The Ohio State University Wexner Medical Center)

  • Sandrine V. Pierre

    (Marshall University)

  • Shubha Gururaja Rao

    (Ohio Northern University)

  • Dan R. Halm

    (Wright State University)

  • Tingting Chen

    (University of Groningen)

  • Panagiotis S. Athanasopoulos

    (University of Groningen)

  • Amalia M. Dolga

    (University of Groningen)

  • Lianbo Yu

    (The Ohio State University)

  • Mahmood Khan

    (The Ohio State University Wexner Medical Center)

  • Harpreet Singh

    (The Ohio State University
    The Ohio State University Wexner Medical Center)

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.

Suggested Citation

  • 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 & Tingti, 2025. "Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55379-4
    DOI: 10.1038/s41467-024-55379-4
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