Figure 3. Intracellular signalling events.

The signalling cascades and intracellular pathways that are used by viruses and bacteria to induce host cell uptake converge on those used in vesicle trafficking. A common theme is the activation of GTPases and the subsequent cytoskeletal changes that aid in the movement of vesicles or in the uptake of pathogens. a | In SNARE-mediated vesicle trafficking and exocytosis, intracellular factors such as the exocyst protein complex and the small GTPase Rab3A are important in the docking of the vesicle to the plasma membrane. Vesicle trafficking also involves the activation of intracellular cytoskeleton effector molecules such as phosphatidylinositol 3-kinase (PI3K) and other small GTPases such as Cdc42. F-actin nucleation mediated by N-WASP (neural Wiskott–Aldrich syndrome protein) and ARP2/3, and microtubule elongation are crucial in trafficking events. Receptor-mediated attachment of viruses such as influenza virus (b) and bacteria such as Yersinia spp. (c) also leads to the signalling and activation of GTPases (such as dynamin, Ras, Rac1 and Cdc42), as well as actin polymerization through the ARP2/3 complex (mediated by N-WASP in bacteria, and N-WASPand intersectin in viruses). PI3K is activated by the binding of certain viruses and bacteria to cell surface receptors, and is also implicated in actin polymerization. AP2, adaptor protein-2; CAS, Crk-associated substrate; CAT2, cationic amino-acid transporter; DAG, diacylglycerol; FAK, focal adhesion kinase; GRB2, growth factor receptor-bound protein-2; MAPK, mitogen-activated protein kinase; PIP₂, phosphatidylinositol-4,5-bisphosphate; PI₄P, phosphatidylinositol 4-phosphate; PKC, protein kinase C; SH2, Src-homology domain-2; SNARE, soluble NSF (N-ethylmaleimide-sensitive fusion protein) accessory protein (SNAP) receptor.