PXD031051

PXD031051 is an original dataset announced via ProteomeXchange.

Title	K2P2.1 shapes morphology and function of brain endothelial cells via actin network remodeling
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-27_18:07:37.715.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ute Distler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-18 02:21:54	ID requested
⏵ 1	2025-07-27 18:07:38	announced

Lichtenberg S, Vinnenberg L, Steffen F, Plegge I, Hanuscheck N, Dobelmann V, Gruchot J, Schroeter CB, Ramachandran H, Wasser B, Bachir D, Nelke C, Franz J, Riethm, ü, ller C, Tenzer S, Distler U, Vogelaar CF, Kusche-Vihrog K, Skryabin BV, Rozhdestvensky TS, Schwab A, Krutmann J, Rossi A, Budde T, Bittner S, Meuth SG, Ruck T, 2.1 shapes the morphology and function of brain endothelial cells via actin network remodeling. Nat Commun, 16(1):6622(2025) [pubmed]

10.1038/s41467-025-61816-9;

submitter keyword: actin remodeling, EAE, Kcnk2, blood-brain-barrier, TREK1,K2P2.1, LC-MS/MS

Tenzer, Stefan
contact affiliation	Institute of Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
contact email	tenzer@uni-mainz.de
lab head
Ute Distler
contact affiliation	University Medical Center Mainz
contact email	ute.distler@uni-mainz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/07/PXD031051

PRIDE project URI

• PRIDE
  1. PXD031051
     1. Label: PRIDE project
     2. Name: K2P2.1 shapes morphology and function of brain endothelial cells via actin network remodeling