Inserm, U1016, Department of Infection, Immunity and Inflammation, Institut Cochin, 75014 Paris, France.
CNRS, UMR 8104, 75014 Paris, France.
Nat Commun. 2017 Jun 1;8:15764. 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 (βAR), 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 βAR 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-βAR 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.
脑膜炎奈瑟菌（脑膜炎球菌）是一种侵袭性细菌病原体，可定植于人体血管，引起血栓性病变和脑膜炎。与内皮细胞建立紧密的相互作用对脑膜炎球菌抵抗血流动力至关重要。两种内皮受体，CD147 和 β2 肾上腺素能受体（βAR），被脑膜炎球菌依次结合以粘附并促进导致血管定植的信号事件，但它们的时空协调尚不清楚。在这里，我们报告 CD147 和 βAR 形成组成型异源寡聚体复合物。支架蛋白肌动蛋白-4 直接结合 CD147 的胞质尾部，并在细菌粘附部位以高度有序的簇形式调节 CD147-βAR 复合物的组装。这个多分子组装过程增加了脑膜炎球菌在切应力下与内皮细胞的结合强度，并为围绕粘附细菌的膜突起的伸长创造了分子平台。因此，细胞受体的特异性组织对宿主-病原体相互作用有重大影响。
