# Tetraspanin-enriched microdomains and endothelial barrier function

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $370,221

## Abstract

Cell-cell and cell-matrix adhesions play essential roles in endothelial barrier function. Various
tetraspanins are expressed in endothelium, form tetraspanin-enriched microdomains with cell
adhesion proteins such as integrins, and regulate endothelial cell adhesion and vascular
permeability. Our early study revealed that tetraspanins are required for maintaining proper
endothelial adhesiveness, endothelial barrier, and vascular permeability. We have demonstrated
that, to sustain vascular stability, tetraspanin-enriched microdomains tune the balance of Rac1
and RhoA small GTPase activities or the balance of cortical actin meshwork and stress fibers to
sustain endothelial cell-cell and cell matrix adhesions. But the in-depth mechanisms by which
tetraspanins regulate endothelial barrier function still remain elusive.
 We will use tetraspanin CD151 as example in this study to elucidate the mechanisms by which
tetraspanin-enriched microdomains regulate endothelial barrier function and vascular permeability.
The overarching hypotheses of this project include that, at the cellular level, CD151 promotes
endothelial barrier function by primarily increasing endothelial cell-matrix interactions, which
subsequently elevates endothelial cell-cell adhesion. Meanwhile, CD151 can also directly
reinforce endothelial cell-cell interaction. At the molecular level, CD151 reinforces cell adhesions
by enhancing the functional accessibility and nanoscale organization of cell adhesion proteins at
endothelial cell surface.
 Specifically, we will first unravel the mechanism by which CD151 reinforces endothelial cell-
matrix adhesion. We will assess both in vitro and in vivo mechanistic roles of CD151 in integrin
activation and accessibility at the basal surface of endothelial cells. Secondly, we will reveal the
mechanism by which CD151 reinforces endothelial cell-cell adhesion. We will assess both in vitro
and in vivo mechanistic roles of CD151 in maintaining structural and functional integrity of
endothelial cell-cell contacts, which directly prevents endothelial hyper-permeability. Finally, we
will delineate the signaling mechanisms by which CD151 reinforces endothelial barrier and
reduces vascular hyper-permeability.
 Hence, the general goal of this project is to understand how CD151 sustains the endothelium
barrier function by assessing both in vitro and in vivo mechanistic roles of CD151 in stabilizing the
structural and functional interactions of endothelium with the underlying basement membrane and
in maintaining the structural and functional integrity of endothelial cell-cell contacts and junctions.
 From these studies, we will understand why and how tetraspanin-enriched microdomains are
important for endothelial barrier function, establish a novel paradigm between vascular
permeability and membrane organization of cell adhesion molecules, and delineate the signaling
axis that governs the fine balance of small GTPases in endothelium. From the in-depth
mechanistic ...

## Key facts

- **NIH application ID:** 9858402
- **Project number:** 5R01HL132553-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** XIN A ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,221
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858402

## Citation

> US National Institutes of Health, RePORTER application 9858402, Tetraspanin-enriched microdomains and endothelial barrier function (5R01HL132553-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858402. Licensed CC0.

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