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Nat Commun. 2017 Jun 1;8:15764. doi: 10.1038/ncomms15764.

Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4.

Maïssa N1,2,3, Covarelli V1,2,3, Janel S4,5,6,7, Durel B1,2,3, Simpson N1,2,3, Bernard SC1,2,3, Pardo-Lopez L1,2,3, Bouzinba-Ségard H1,2,3, Faure C1,2,3, Scott MGH1,2,3, Coureuil M8,9,10, Morand PC1,2,10, Lafont F4,5,6,7, Nassif X8,9,10,11, Marullo S1,2,3, Bourdoulous S1,2,3.

Author information

1
Inserm, U1016, Department of Infection, Immunity and Inflammation, Institut Cochin, 75014 Paris, France.
2
CNRS, UMR 8104, 75014 Paris, France.
3
Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
4
Cellular Microbiology and Physics of infection, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 59000 Lille, France.
5
CNRS, UMR 8204, 59000 Lille, France.
6
Inserm, U1019, 59000 Lille, France.
7
Université de Lille, 59000 Lille, France.
8
Inserm, unité U1151, Institut-Necker-Enfants-Malades, 75015 Paris, France.
9
CNRS, UMR 8253, 75015 Paris, France.
10
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 75006 Paris, France.
11
Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, 75015 Paris, France.

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 (β2AR), 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 β2AR 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-β2AR 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.

PMID:
28569760
PMCID:
PMC5461506
DOI:
10.1038/ncomms15764
[Indexed for MEDLINE]
Free PMC Article

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