Meningococcus Hijacks a β2-Adrenoceptor/β-Arrestin Pathway to Cross Brain Microvasculature Endothelium

Coureuil, M. et al. Cell 2010 (143): 1149–1160

Speaker: Chun-Hsien Fei (費俊憲)                               Time: 15:10~16:00, Apr, 20, 2011

Commentator: Prof. Lien-I Hor (何漣漪 老師)          Place: Room 601

Abstract

        Neisseria meningitidis, or meningococcus, is well known as an important pathogen in epidemic meningitis and sepsis. N. meningitidis causes morbidity and mortality in childhood. After blood invasion, meningococcus adheres to human brain endothelial cells via type-IV-pilus and initiates signal pathway result in the impaired intracellular junction, allowing their crossing of endothelium cells. However, how the receptor activated by N. meningitidis is still unknown. In this paper, the authors reported that meningococcus activate β2-adrenoceptor/β-arrestin signaling pathway in endothelial cells. Immunoflorescent staining showed that β-arrestin is required for the formation of “honeycomb” complex to resist shear stress. Treatment of β2-adrenoceptor agonist isoproterenol, which induced receptor desensitization and endocytosis¹, resulted in impaired bacterium growth and adhesion under flow. Isoproterenol treatment also reduced recruitment of endothelial cell adhesion molecules, such as VE-cadherin, avoiding depletion of intracellular junctions. Furthermore, the mutant form of β-arrestin and β2-adrenoceptor/β-arrestin siRNA reduced recruitment of src and adhesion molecules. In conclusion, N. meningitidis activates biased β2-adrenoceptor/β-arrestin pathway which provides docking site for src and junctional proteins. Src mediated cytoskeletal reorganization stabilizes adhesion between bacteria and endothelial cells². Delocaliztaion of junctionalproteins results in gaps that crossed by meningococcus. β2-adrenoceptor agonist induced endocytosis prevents N. meningitidis adhesion and crossing of endothelial barrier. The information discovered in this paper could provide new approaches to treatment and prevention of N. meningitidisinfection.

References

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2.      Hoffmann, I. et al. Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial cells by Neisseria meningitidis. Journal of Cell Biology. 2001 (155): 133–143.