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Differential role for rapid proteostasis in Rho GTPase-mediated control of quiescent endothelial integrity.


ABSTRACT: Endothelial monolayer permeability is regulated by actin dynamics and vesicular traffic. Recently, ubiquitination was also implicated in the integrity of quiescent endothelium, as it differentially controls the localization and stability of adhesion and signaling proteins. However, the more general effect of fast protein turnover on endothelial integrity is not clear. Here, we found that inhibition of E1 ubiquitin ligases induces a rapid, reversible loss of integrity in quiescent, primary human endothelial monolayers, accompanied by increased F-actin stress fibers and the formation of intercellular gaps. Concomitantly, total protein and activity of the actin-regulating GTPase RhoB, but not its close homolog RhoA, increase ∼10-fold in 5 to 8 h. We determined that the depletion of RhoB, but

SUBMITTER: Podieh F 

PROVIDER: S-EPMC10124901 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature