Figure 8
Model of C. jejuni internalization. C. jejuni invasion of host cells. Step 1: C. jejuni binds to fibronectin (Fn) via the two C. jejuni Fn binding proteins CadF (blue dots) and FlpA (yellow dots) [43, 44] causing activation of the α5β1 integrin receptors and the epidermal growth factor receptor (EGFR) [27, 45]. Step 2: Activation of the α5β1 integrin leads to the recruitment and partial activation of FAK and paxillin [27, 46]. Step 3: The delivery of the Campylobacter invasion antigens (e.g., CiaD shown in red) to the host cell [16, 19, 27, 47] leads to the maximal activation of key components of the focal complex (i.e., FAK, paxillin, vinculin, p130Cas, Src, and the CrkII/DOCK-180/ELMO complex) [27,28,45, Konkel et. al, Invasion of epithelial cells by Campylobacter jejuni is independent of caveolin-1, In Submission]. Step 4: Focal complex activation, in conjunction with CiaD, leads to the phosphorylation of Erk 1/2. Caveolin-1, Vav2, Rac1, and Cdc42 are also activated following focal complex activation [27, 28, 45]. Step 5: Activation of Erk 1/2 and Src leads to the phosphorylation of cortactin, which allows for the Rho GTPases Rac1 and Cdc42 to activate N-WASP associated with phosphorylated cortactin, promoting actin cytoskeletal reorganization. Highlighted in this model is the role of CiaD in C. jejuni internalization. Specifically, CiaD is necessary for the maximal activation of the Erk 1/2 and cortactin signaling pathways. Components of the focal complex and focal complex associated proteins are shown in blue. The newly identified components of the C. jejuni invasion complex are shown in green.