MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression

Juan F Aranda, Natalia Reglero-Real, Beatriz Marcos-Ramiro, Ana Ruiz-Sáenz, Laura Fernández-Martín, Miguel Bernabé-Rubio, Leonor Kremer, Anne J Ridley, Isabel Correas, Miguel A Alonso, Jaime Millán

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)

Abstract

The endothelium maintains a barrier between blood and tissue that becomes more permeable during inflammation. Membrane rafts are ordered assemblies of cholesterol, glycolipids, and proteins that modulate proinflammatory cell signaling and barrier function. In epithelial cells, the MAL family members MAL, MAL2, and myeloid-associated differentiation marker (MYADM) regulate the function and dynamics of ordered membrane domains. We analyzed the expression of these three proteins in human endothelial cells and found that only MYADM is expressed. MYADM was confined in ordered domains at the plasma membrane, where it partially colocalized with filamentous actin and cell-cell junctions. Small interfering RNA (siRNA)-mediated MYADM knockdown increased permeability, ICAM-1 expression, and leukocyte adhesion, all of which are features of an inflammatory response. Barrier function decrease in MYADM-silenced cells was dependent on ICAM-1 expression. Membrane domains and the underlying actin cytoskeleton can regulate each other and are connected by ezrin, radixin, and moesin (ERM) proteins. In endothelial cells, MYADM knockdown induced ERM activation. Triple-ERM knockdown partially inhibited ICAM-1 increase induced by MYADM siRNA. Importantly, ERM knockdown also reduced ICAM-1 expression in response to the proinflammatory cytokine tumor necrosis factor-α. MYADM therefore regulates the connection between the plasma membrane and the cortical cytoskeleton and so can control the endothelial inflammatory response.

Original languageEnglish
Pages (from-to)483-94
Number of pages12
JournalMolecular Biology of the Cell
Volume24
Issue number4
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Animals
  • Biological Transport
  • Cell Adhesion
  • Cytoskeletal Proteins
  • Dogs
  • Gene Expression Regulation
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1
  • Madin Darby Canine Kidney Cells
  • Membrane Microdomains
  • Membrane Proteins
  • Microfilament Proteins
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • RNA, Small Interfering
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, Non-U.S. Gov't

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