The Calcium Pump ATP2B1/PMCA1 Regulates CNS Vascular Development by Facilitating Norrin- and WNT7A/B-induced Frizzled4 signaling.

ABSTRACT: Frizzled4 (FZD4) is a receptor for Norrin and WNT7A/B ligands, is expressed in endothelial cells (ECs), is required for blood-CNS-barrier function as well as CNS angiogenesis, and transduces β-catenin-dependent signaling. Despite its fundamental importance in neurovascular biology, including as drug target, the molecular mechanisms governing FZD4 regulation remain poorly understood. Here, we employed proximity biotinylation to identify proteins that regulate FZD4. We identified ATPase Plasma Membrane Ca²⁺ Transporting 1 (ATP2B1, also known as PMCA1) as a FZD4 proximity interactor. Functional analyses revealed that ATP2B1 depletion increased EC Ca²⁺ and significantly attenuated Norrin/Frizzled4 signaling. These effects of Atp2b1 deficiency were recapitulated by

SUBMITTER: Jo HN 

PROVIDER: S-EPMC12330718 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature