Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β<sub>2</sub>-adrenoceptor clusters assembled by alpha-actinin-4.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28569760.
- Also identified by DOI 10.1038/ncomms15764 and PMC identifier 5461506.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist haemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic receptor (β<sub>2</sub>AR), are sequentially engaged by meningococci to adhere and promote signalling events leading to vascular colonization, but their spatiotemporal coordination is unknown. Here we report that CD147 and β<sub>2</sub>AR form constitutive hetero-oligomeric complexes. The scaffolding protein α-actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147-β<sub>2</sub>AR complexes in highly ordered clusters at bacterial adhesion sites. This multimolecular assembly process increases the binding strength of meningococci to endothelial cells under shear stress, and creates molecular platforms for the elongation of membrane protrusions surrounding adherent bacteria. Thus, the specific organization of cellular receptors has major impacts on host-pathogen interaction.
Medical subject headings
- Actinin
- Basigin
- Host-Pathogen Interactions
- Neisseria meningitidis
- Receptors, Adrenergic, beta-2