Sanghvi Shridhar, Sridharan Divya, Evans Parker, Dougherty Julie, Szteyn Kalina, Gabrilovich Denis, Dyta Mayukha, Weist Jessica, Pierre Sandrine V, Gururaja Rao Shubha, Halm Dan R, Chen Tingting, Athanasopoulos Panagiotis S, Dolga Amalia M, Yu Lianbo, Khan Mahmood, Singh Harpreet
Department of Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, OH, USA.
Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Nat Commun. 2025 Jan 2;16(1):42. doi: 10.1038/s41467-024-55379-4.
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) in the membrane of EVs. Furthermore, we establish that BK is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BK in functioning as gatekeepers and maintaining EV-mediated signaling.
细胞外囊泡（EVs）与细胞间通讯、免疫反应、病毒致病性、心血管疾病、神经紊乱以及癌症进展相关。细胞外囊泡将蛋白质、代谢物和核酸传递到受体细胞中，以有效改变其生理和生物学反应。在从供体细胞运输到受体细胞的过程中，细胞外囊泡面临不同的离子浓度，这可能对其完整性有害并影响其货物含量。已知细胞外囊泡在其膜中具有离子通道和转运蛋白，但这些通道在细胞外囊泡中的功能和作用均不为人所知。在本研究中，我们在细胞外囊泡膜中发现了一种功能性钙激活大电导钾通道（BK）。此外，我们证实BK对于细胞外囊泡的结构和功能完整性至关重要。总之，这些发现确立了诸如BK等离子通道在作为守门人以及维持细胞外囊泡介导的信号传导中所起的关键作用。
