Knock twice before invading

Knock twice before invading eisseria meningitidis , also known as meningococcus, is a pathogen with a nasty habit of forcing normally nonphagocytic endothelial cells to engulf it, allowing the bacterium to penetrate cellular barriers. Hoffmann et al. now demonstrate on page 133 that N. meningitidis activates two distinct signaling pathways in host cells to cause actin cytoskeleton reorganization and engulfment of the bacterium. N ErbB2 (green) and invading bacteria (red) colocalize. Adherence of the bacteria to endothelial cells causes massive and specific aggregation of the receptor tyrosine kinase ErbB2, which normally transduces signals by heterodimerization with other ErbB-like receptors. However, during N. meningitidis invasion, ErbB2 forms homodimers that, once autophosphorylated, can activate the src kinase. Inhibiting this process prevents internalization of the pathogen, but does not block the characteristic actin rearrangements induced by the bacterium. Blocking both ErbB2/src signaling and actin polymerization completely prevents bacterial engulfment, indicating that the two pathways are independent, but that both are required for invasion. While it is possible that ErbB2 is a receptor for the bacterial pilus, the data are also consistent with the recruitment of ErbB2 as part of a multiprotein complex that includes an unknown receptor. In separate work, Bierne et al. (page 101) characterized phagocytosis induced by the pathogen Listeria monocytoge-nes , and observed actin cytoskeleton remodeling that is apparently mediated by the activation and deactivation of cofilin. ᭿ Disgorging the MVB he multivesicular body (MVB), a cluster of vesicles surrounded by a limiting membrane, is a ubiquitous but poorly understood structure in eukaryotic cells. On page 53, Kleijmeer et al. present the first evidence that the MVB can be used as a temporary storage depot for membranes and membrane proteins, which can then be deployed rapidly to the surface of the cell. The work also helps to explain how certain antigens are presented to initiate a primary T cell response. Previous work on this problem had left a basic topological question unresolved: how does antigen-presenting MHC II move from the internal vesicles of the MVB to the exterior surface of the plasma membrane? T A transformation from blobs (top) to tubules (bottom) helps load antigen. The authors found that in immature cultured dendritic cells, MHC II is concentrated in the internal vesicles of MVBs, while the peptide-loading accessory molecule DM is found mostly in the MVB limiting membrane. When the cells are activated, the internal vesicles fuse with the limiting …