Related Experiment Video

Updated: May 16, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth and assemble adherens junctions

Yulia A Komarova1, Fei Huang, Melissa Geyer

  • 1Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA. ykomarov@uic.edu

Molecular Cell
|November 20, 2012
PubMed

Insights

Vascular endothelial (VE)-cadherin adhesion loss activates signaling pathways, leading to calcium release and calcineurin activation. This process regulates end binding protein 3 (EB3) phosphorylation, controlling microtubule dynamics and adherens junction assembly in endothelial cells.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Vascular endothelial (VE)-cadherin mediates endothelial barrier integrity through adherens junctions (AJs).
  • VE-cadherin adhesion is crucial for maintaining endothelial cell-cell junctions and regulating barrier permeability.

Purpose of the Study:

  • To elucidate the signaling pathways downstream of VE-cadherin homophilic adhesion loss.
  • To investigate the role of calcium homeostasis and end binding protein 3 (EB3) phosphorylation in AJ assembly.

Main Methods:

  • Investigated signaling cascades including Src, phospholipase C (PLC)γ2, and calcineurin (CaN) activation.
  • Analyzed calcium (Ca2+) release from endoplasmic reticulum (ER) stores.
  • Studied the phosphorylation status of EB3 at serine 162 and its impact on microtubule (MT) dynamics and AJ assembly.

Main Results:

  • Loss of VE-cadherin adhesion triggered Src and PLCγ2 activation, leading to Ca2+ release and CaN activation.
  • CaN activity downregulation induced EB3 phosphorylation at S162, destabilizing EB3 dimers and suppressing MT growth.
  • Phospho-defective S162A EB3 mutant promoted MT growth and AJ disassembly in confluent endothelial cells.

Conclusions:

  • VE-cadherin outside-in signaling regulates endothelial barrier function by modulating cytosolic Ca2+ homeostasis and EB3 phosphorylation.
  • EB3 phosphorylation is a critical phospho-switch controlling microtubule dynamics and adherens junction assembly.
  • VE-cadherin homophilic interactions are pivotal in maintaining endothelial barrier integrity via regulation of microtubule dynamics.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Visualizing Neuroblast Cytokinesis During C. elegans Embryogenesis09:52

Visualizing Neuroblast Cytokinesis During C. elegans Embryogenesis

Published on: March 12, 2014

Related Concept Videos

Adherens Junctions01:24

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
The endothelial cells...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...