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

被引：3

作者：

Sanghvi, Shridhar ^{[1
,2
]}

Sridharan, Divya ^{[3
]}

Evans, Parker ^{[4
]}

Dougherty, Julie ^{[3
]}

Szteyn, Kalina ^{[2
]}

Gabrilovich, Denis ^{[1
]}

Dyta, Mayukha ^{[2
]}

Weist, Jessica ^{[3
]}

Pierre, Sandrine V. ^{[5
]}

Gururaja Rao, Shubha ^{[6
]}

Halm, Dan R. ^{[7
]}

Chen, Tingting ^{[8
]}

Athanasopoulos, Panagiotis S. ^{[8
]}

Dolga, Amalia M. ^{[8
]}

Yu, Lianbo ^{[9
]}

Khan, Mahmood ^{[3
]}

Singh, Harpreet ^{[1
,2
]}

机构：

[1] Ohio State Univ, Dept Mol Cellular & Dev Biol, Columbus, OH 43210 USA

[2] Ohio State Univ, Wexner Med Ctr, Dept Physiol & Cell Biol, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Emergency Med, Div Basic & Translat Res, Wexner Med Ctr, Columbus, OH 43210 USA

[4] Ohio State Univ, Dept Mech & Aerosp Engn, Columbus, OH USA

[5] Marshall Univ, Joan C Edwards Sch Med, Dept Biomed Sci, Huntington, WV USA

[6] Ohio Northern Univ, Raabe Coll Pharm, Dept Pharmaceut & Biomed Sci, Ada, OH USA

[7] Wright State Univ, Dept Neurosci Cell Biol & Physiol, Dayton, OH USA

[8] Univ Groningen, Groningen Res Inst Pharm, Dept Mol Pharmacol, Groningen, Netherlands

[9] Ohio State Univ, Dept Biomed Informat, Columbus, OH USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

CA2+-ACTIVATED K+ CHANNELS; CELL EXOSOMES; PROTEIN; MECHANISM; CLIC1; MODULATION;

D O I：

10.1038/s41467-024-55379-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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