Sousa Sandra, Cabanes Didier, El-Amraoui Aziz, Petit Christine, Lecuit Marc, Cossart Pascale
Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris CEDEX 15, France.
J Cell Sci. 2004 Apr 15;117(Pt 10):2121-30. doi: 10.1242/jcs.01066.
Listeria monocytogenes is a bacterial pathogen with the capacity to invade non-phagocytic cells. This dynamic process involves coordinated membrane remodelling and actin cytoskeleton rearrangements. Although some of the molecular factors promoting these events have been identified, the driving force allowing internalization is unknown. One of the receptors for L. monocytogenes on epithelial cells is E-cadherin, a transmembrane protein normally involved in homophilic interactions that allow cell-cell contacts at the adherens junctions. E-cadherin has to be connected to the actin cytoskeleton to mediate strong cell-cell adhesion and to trigger Listeria entry; alpha- and beta-catenins play key roles in these processes. We have recently identified an unconventional myosin, myosin VIIa and its ligand vezatin, at the adherens junctions of polarized epithelial cells. Here, we demonstrate by pharmacological and genetic approaches that both myosin VIIa and vezatin are crucial for Listeria internalization. These results provide the first evidence for the role of an unconventional myosin in bacterial internalization and a novel example of the exploitation of mammalian proteins, by a pathogen, to establish a successful infection.
单核细胞增生李斯特菌是一种能够侵入非吞噬细胞的细菌病原体。这一动态过程涉及协调的膜重塑和肌动蛋白细胞骨架重排。尽管已经确定了一些促进这些事件的分子因素，但内化的驱动力尚不清楚。上皮细胞上单核细胞增生李斯特菌的受体之一是E-钙黏蛋白，它是一种跨膜蛋白，通常参与同型相互作用，使细胞在黏附连接处实现细胞间接触。E-钙黏蛋白必须与肌动蛋白细胞骨架相连，以介导强细胞间黏附并触发李斯特菌进入；α-连环蛋白和β-连环蛋白在这些过程中起关键作用。我们最近在极化上皮细胞的黏附连接处发现了一种非常规肌球蛋白，即肌球蛋白VIIa及其配体vezatin。在这里，我们通过药理学和遗传学方法证明，肌球蛋白VIIa和vezatin对李斯特菌的内化至关重要。这些结果首次证明了非常规肌球蛋白在细菌内化中的作用，以及病原体利用哺乳动物蛋白建立成功感染的新例子。
