Endothelial deletion of TBK1 contributes to BRB dysfunction via CXCR4 phosphorylation suppression.

ABSTRACT: Blood-retinal barrier (BRB) dysfunction has been recognized as an early pathological feature in common eye diseases that cause blindness. The breakdown of endothelial cell-to-cell junctions is the main reason for BRB dysfunction, yet our understanding of junctional modulation remains limited. Here, we demonstrated that endothelial-specific deletion of TBK1 (Tbk1^ΔEC) disrupted retinal vascular development, and induced vascular leakage. LC-MS/MS proteomic analysis was used to identify candidate substrates of TBK1. We found that TBK1 interacted with CXCR4, and the phosphorylation level of CXCR4-Serine 355 (Ser355) was decreased in Tbk1^ΔEC retina samples. Furthermore, TBK1-mediated phosphorylation of CXCR4 at Ser355 played an indispensable role in maintaining endothelial

SUBMITTER: Zhao B 

PROVIDER: S-EPMC9616849 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature