Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β 2 -adrenoceptor clusters assembled by alpha-actinin-4

• Published in: Nature communications Vol. 8; p. 15764
• Main Authors: Maïssa, Nawal, Covarelli, Valentina, Janel, Sébastien, Durel, Beatrice, Simpson, Nandi, Bernard, Sandra C, Pardo-Lopez, Liliana, Bouzinba-Ségard, Haniaa, Faure, Camille, Scott, Mark G H, Coureuil, Mathieu, Morand, Philippe C, Lafont, Frank, Nassif, Xavier, Marullo, Stefano, Bourdoulous, Sandrine
• Format: Journal Article
• Language: English
• Published: England 01-06-2017
• Subjects: Actinin - metabolism; Bacterial Adhesion - physiology; Basigin - genetics; Basigin - metabolism; Endothelial Cells - metabolism; Endothelial Cells - microbiology; Host-Pathogen Interactions - physiology; Humans; Multiprotein Complexes - metabolism; Neisseria meningitidis - metabolism; Neisseria meningitidis - pathogenicity; Receptors, Adrenergic, beta-2 - genetics; Receptors, Adrenergic, beta-2 - metabolism
• ISSN: 2041-1723
• DOI: 10.1038/ncomms15764

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
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
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
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.