Dataset Information

K2P2.1 shapes morphology and function of brain endothelial cells via actin network remodeling

ABSTRACT: K2P2.1 (gene: Kcnk2), a two-pore domain potassium channel, is an important regulator of leukocyte transmigration across the blood-brain barrier. However, the underlying molecular mechanisms remain poorly characterized. We here show that Kcnk2-/- mouse brain microvascular endothelial cells (MBMECs) show an altered surface morphology with increased formation of membrane protrusions. Those protrusions express clusters of cell adhesion molecules facilitating leukocyte adhesion and migration in vitro and in vivo. Kcnk2-/- MBMECs further display enhanced cortical stiffness and stress fiber formation, indicating altered cellular actin dynamics. Accordingly, we observe K2P2.1 redistribution to intracellular actin fibers and activation of actin modulating proteins (Cofilin1, Arp2/3). Pharmacological inhibition of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2), an essential regulator of those proteins, reverse the Kcnk2-/- phenotype. In the mechanosensitive conformation, K2P2.1 shields PI(4,5)P2 from interaction with other actin regulatory proteins. Actin rearrangements are induced by stimulus-related K2P2.1 internalization. Thus, K2P2.1-mediated regulatory processes are essential for actin dynamics, fast, reversible, and pharmacologically targetable.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain Microvascular Endothelial Cell

SUBMITTER: Ute Distler

LAB HEAD: Tenzer, Stefan

PROVIDER: PXD031051 | Pride | 2025-07-28

REPOSITORIES: Pride

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The potassium channel K2P2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling.

Lichtenberg Stefanie S Vinnenberg Laura L Steffen Falk F Plegge Isabelle I Hanuscheck Nicholas N Dobelmann Vera V Gruchot Joel J Schroeter Christina B CB Ramachandran Haribaskar H Wasser Beatrice B Bachir Derya D Nelke Christopher C Franz Jonas J Riethmüller Christoph C Tenzer Stefan S Distler Ute U Vogelaar Christina Francisca CF Kusche-Vihrog Kristina K Skryabin Boris V BV Rozhdestvensky Timofey S TS Schwab Albrecht A Krutmann Jean J Rossi Andrea A Budde Thomas T Bittner Stefan S Meuth Sven G SG Ruck Tobias T

Nature communications 20250718 1

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 ob ...[more]

PMID: 40681505

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K2P2.1 shapes morphology and function of brain endothelial cells via actin network remodeling

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The potassium channel K<sub>2P</sub>2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling.

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Dataset Information

K2P2.1 shapes morphology and function of brain endothelial cells via actin network remodeling

Dataset's files

Publications

The potassium channel K&lt;sub&gt;2P&lt;/sub&gt;2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling.

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OmicsDI is part of the ELIXIR infrastructure

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The potassium channel K<sub>2P</sub>2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling.