The E3 ubiquitin ligase MARCH3 controls the endothelial barrier

Cell–cell contacts coordinate the endothelial barrier function in response to external cues. To identify new mediators involved in cytokine‐promoted endothelial permeability, we screened a siRNA library targeting E3 ubiquitin ligases. Here, we report that silencing of the late endosome/lysosomal mem...

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Veröffentlicht in:FEBS letters 2016-10, Vol.590 (20), p.3660-3668
Hauptverfasser: Leclair, Héloïse M., André‐Grégoire, Gwennan, Treps, Lucas, Azzi, Sandy, Bidère, Nicolas, Gavard, Julie
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Sprache:eng
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Zusammenfassung:Cell–cell contacts coordinate the endothelial barrier function in response to external cues. To identify new mediators involved in cytokine‐promoted endothelial permeability, we screened a siRNA library targeting E3 ubiquitin ligases. Here, we report that silencing of the late endosome/lysosomal membrane‐associated RING‐CH‐3 (MARCH3) enzyme protects the endothelial barrier. Furthermore, transcriptome analysis unmasked the upregulation of the tight junction‐encoding gene occludin (OCLN) in MARCH3‐depleted cells. Indeed, MARCH3 silencing results in the strengthening of cell‐cell contacts, as evidenced by the accumulation of junctional proteins. From a molecular standpoint, the FoxO1 forkhead transcription repressor was inactivated in the absence of MARCH3. This provides a possible molecular link between MARCH3 and the signaling pathway involved in regulating the expression of junctional proteins and barrier integrity.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12417