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Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
Published on: October 4, 2019
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Podosome formation impairs endothelial barrier function by sequestering zonula occludens proteins.
Yan-Ning Rui1, Yawen Chen1,2, Yichen Guo1,2
1Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
Journal of Cellular Physiology
|October 23, 2019
Summary
Endothelial podosomes sequester tight junction proteins, weakening cell barriers and increasing permeability. This novel function of podosomes negatively impacts cerebrovascular integrity.
Area of Science:
- Cell Biology
- Endothelial Cell Biology
- Cerebrovascular Research
Background:
- Tight junctions (TJs) maintain cerebrovascular integrity.
- The function of endothelial podosomes is largely unknown.
- Podosomes and TJs are cell surface structures in endothelial cells.
Purpose of the Study:
- To investigate the function of endothelial podosomes.
- To explore the relationship between podosomes and TJs in human brain endothelial cells.
- To determine the role of ZO proteins in podosome formation and TJ integrity.
Main Methods:
- PMA treatment of human brain endothelial cells.
- Immunofluorescence and co-localization studies for ZO-1, ZO-2, and cortactin.
- Assessment of endothelial cell permeability.
- Inhibition of podosome formation using PP2.
Main Results:
- PMA treatment induced ZO-1 and ZO-2 localization to podosomes.
- ZO proteins are essential for podosome formation and function.
- Podosomal ZO proteins are relocated from the plasma membrane, interacting with cortactin.
- Podosome formation led to weakened TJs and increased endothelial permeability.
- PP2 treatment attenuated the effect of podosomes on TJ integrity.
Conclusions:
- Endothelial podosomes negatively regulate TJ formation and endothelial barrier integrity.
- Podosomal sequestration of ZO proteins is a key mechanism for barrier disruption.
- This finding reveals a novel role for podosomes in cerebrovascular diseases.
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