Host epac1 modulates rickettsial adhesion to vascular endothelial cells via regulation of anxa2 y23 phosphorylation

Zhengchen Su, Thomas Shelite, Yuan Qiu, Qing Chang, Maki Wakamiya, Jiani Bei, Xi He, Changcheng Zhou, Yakun Liu, Emmanuel Nyong, Yuejin Liang, Angelo Gaitas, Tais B. Saito, Bin Gong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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. Conclusion: 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.

Original languageEnglish (US)
Article number1307
JournalPathogens
Volume10
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • Annexin A2
  • Bacterial adhesion
  • EPAC1
  • Endothelial cell
  • Fluidic force microscopy
  • Rickettsia
  • Single living cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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