Junctional Localization of Septin 2 Is Required for Organization of Junctional Proteins in Static Endothelial Monolayers

Joanna Kim, John A. Cooper

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

OBJECTIVE: Septin 2 is localized at junctions in human microvascular endothelial monolayers. The junctional localization of septin 2 is necessary for organization of cell-cell adhesion proteins of endothelial cells. APPROACH AND RESULTS: Septin 2 was depleted at junctions by suppression of expression using shRNA, treatment with inflammatory cytokine, TNF (tumor necrosis factor)-α, and ectopic overexpression of septin 2 phosphatidylinositol 4,5-bisphosphate binding mutant defect in interaction with plasma membrane. Under those conditions, organizations and expression levels of various junctional proteins were analyzed. Confocal images of immunofluorescence staining showed substantial disorganization of adherens junctional proteins, nectin-2 and afadin, TJP (tight junction protein), ZO (zonula occludens)-1, and intercellular adhesion protein, PECAM-1 (platelet-endothelial cell adhesion molecule-1). Immunoblots for those proteins did not show significant changes in expression except for nectin-2 that highly increased in expression. Significant differential gene expression profiles and biological pathway analysis by septin 2 suppression and by TNF-α treatment using RNA-seq showed common overlapping pathways. The commonalities in expression may be consistent with the similar effects on the overall organization of cell-cell adhesion proteins. CONCLUSIONS: Localization of septin 2 at cell junctions are required for the arrangement of junctional proteins and the integrity of the barrier formed by endothelial monolayers

Original languageEnglish
Pages (from-to)346-359
Number of pages14
JournalArteriosclerosis, thrombosis, and vascular biology
Volume41
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Adherens junctions
  • Cadherins
  • Cytokines
  • Endothelial cells
  • Nectins

Fingerprint

Dive into the research topics of 'Junctional Localization of Septin 2 Is Required for Organization of Junctional Proteins in Static Endothelial Monolayers'. Together they form a unique fingerprint.

Cite this