Author
Listed:
- Stefanie Lichtenberg
(Heinrich Heine University Düsseldorf
Heinrich Heine University Düsseldorf)
- Laura Vinnenberg
(Heinrich Heine University Düsseldorf)
- Falk Steffen
(University Medical Center of the Johannes Gutenberg-University Mainz)
- Isabelle Plegge
(University of Muenster)
- Nicholas Hanuscheck
(University Medical Center of the Johannes Gutenberg-University Mainz)
- Vera Dobelmann
(Heinrich Heine University Düsseldorf)
- Joel Gruchot
(Heinrich Heine University Düsseldorf)
- Christina B. Schroeter
(Heinrich Heine University Düsseldorf)
- Haribaskar Ramachandran
(Core Unit Model Development Düsseldorf)
- Beatrice Wasser
(University Medical Center of the Johannes Gutenberg-University Mainz)
- Derya Bachir
(Heinrich Heine University Düsseldorf)
- Christopher Nelke
(Heinrich Heine University Düsseldorf)
- Jonas Franz
(University of Göttingen
University of Muenster)
- Christoph Riethmüller
(University of Muenster)
- Stefan Tenzer
(University Medical Center of the Johannes-Gutenberg University Mainz)
- Ute Distler
(University Medical Center of the Johannes-Gutenberg University Mainz)
- Christina Francisca Vogelaar
(University Medical Center of the Johannes Gutenberg-University Mainz)
- Kristina Kusche-Vihrog
(Partner Site Hamburg/Lübeck/Kiel)
- Boris V. Skryabin
(University of Münster)
- Timofey S. Rozhdestvensky
(University of Münster)
- Albrecht Schwab
(University of Münster)
- Jean Krutmann
(Core Unit Model Development Düsseldorf)
- Andrea Rossi
(Core Unit Model Development Düsseldorf)
- Thomas Budde
(University of Münster)
- Stefan Bittner
(University Medical Center of the Johannes Gutenberg-University Mainz)
- Sven G. Meuth
(Heinrich Heine University Düsseldorf)
- Tobias Ruck
(Heinrich Heine University Düsseldorf
Ruhr University Bochum, BG University Hospital Bergmannsheil)
Abstract
K2P2.1 (gene: Kcnk2), a two-pore-domain potassium channel, regulates leukocyte transmigration across the blood-brain barrier by a yet unknown mechanism. We demonstrate that Kcnk2−/− mouse brain microvascular endothelial cells (MBMECs) exhibit an altered cytoskeletal structure and surface morphology with increased formation of membrane protrusions. Cell adhesion molecules cluster on those protrusions and facilitate leukocyte adhesion and migration in vitro and in vivo. We observe downregulation of K2P2.1 and activation of actin modulating proteins (cofilin 1, Arp2/3) in inflamed wildtype MBMECs. In the mechanosensitive conformation, K2P2.1 shields the phospholipid PI(4,5)P2 from interaction with other actin regulatory proteins, especially cofilin 1. Consequently, after stimulus-related K2P2.1 downregulation and dislocation from PI(4,5)P2, actin rearrangements are induced. Thus, K2P2.1-mediated regulatory processes are essential for actin dynamics, fast, reversible, and pharmacologically targetable.
Suggested Citation
Stefanie Lichtenberg & Laura Vinnenberg & Falk Steffen & Isabelle Plegge & Nicholas Hanuscheck & Vera Dobelmann & Joel Gruchot & Christina B. Schroeter & Haribaskar Ramachandran & Beatrice Wasser & De, 2025.
"The potassium channel K2P2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling,"
Nature Communications, Nature, vol. 16(1), pages 1-17, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61816-9
DOI: 10.1038/s41467-025-61816-9
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