Dataset Information

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.

ABSTRACT:

Introduction

Intracellular cAMP receptor exchange proteins directly activated by cAMP 1 (EPAC1) regulate obligate intracellular parasitic bacterium rickettsial adherence to and invasion into vascular endothelial cells (ECs). However, underlying precise mechanism(s) remain unclear. The aim of the study is to dissect the functional role of the EPAC1-ANXA2 signaling pathway during initial adhesion of rickettsiae to EC surfaces.

Methods

In the present study, an established system that is anatomically based and quantifies bacterial adhesion to ECs in vivo was combined with novel fluidic force microscopy (FluidFM) to dissect the functional role of the EPAC1-ANXA2 signaling pathway in rickettsiae-EC adhesion.

Results

The deletion of the EPAC1 gene impedes rickettsial binding to endothelium in vivo. Rickettsial OmpB shows a host EPAC1-dependent binding strength on the surface of a living brain microvascular EC (BMEC). Furthermore, ectopic expression of phosphodefective and phosphomimic mutants replacing tyrosine (Y) 23 of ANXA2 in ANXA2-knock out BMECs results in different binding force to reOmpB in response to the activation of EPAC1.

Conclusions

EPAC1 modulates rickettsial adhesion, in association with Y23 phosphorylation of the binding receptor ANXA2. Underlying mechanism(s) should be further explored to delineate the accurate role of cAMP-EPAC system during rickettsial infection.

SUBMITTER: Su Z

PROVIDER: S-EPMC8537355 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.

Su Zhengchen Z Shelite Thomas R TR Qiu Yuan Y Chang Qing Q Wakamiya Maki M Bei Jiani J He Xi X Zhou Changcheng C Liu Yakun Y Nyong Emmanuel E Liang Yuejin Y Gaitas Angelo A Saito Tais B TB Gong Bin B

Pathogens (Basel, Switzerland) 20211012 10

<h4>Introduction</h4>Intracellular cAMP receptor exchange proteins directly activated by cAMP 1 (<i>EPAC1</i>) regulate obligate intracellular parasitic bacterium rickettsial adherence to and invasion into vascular endothelial cells (ECs). However, underlying precise mechanism(s) remain unclear. The aim of the study is to dissect the functional role of the <i>EPAC1-ANXA2</i> signaling pathway during initial adhesion of rickettsiae to EC surfaces.<h4>Methods</h4>In the present study, an establish ...[more]

PMID: 34684255

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Dataset Information

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.

Introduction

Methods

Results

Conclusions

Publications

Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.

Similar Datasets

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