The potassium channel K2P2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling
Abstract
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.
Article Details
Authors (27)
Stefanie Lichtenberg
Laura Vinnenberg
Falk Steffen
Isabelle Plegge
Nicholas Hanuscheck
Vera Dobelmann
Joel Gruchot
Christina B. Schroeter
Department of Cell Biology, Harvard Medical School
Haribaskar Ramachandran
Beatrice Wasser
Derya Bachir
Christopher Nelke
Jonas Franz
Christoph Riethmüller
Stefan Tenzer
Ute Distler
Christina Francisca Vogelaar
Kristina Kusche-Vihrog
Boris V. Skryabin
Timofey S. Rozhdestvensky
Albrecht Schwab
Jean Krutmann
Andrea Rossi
Genome Engineering and Model Development Lab, Institut für umweltmedizinische Forschung-Leibniz Research Institute for Environmental Medicine
Thomas Budde
Stefan Bittner
Sven G. Meuth
Department of Neurology, Heinrich-Heine University Düsseldorf
Tobias Ruck