Traffic Report Surfing Through a Sea of Sharks: Report on the British Society for Cell Biology Meeting on ‘Signaling and Cytoskeletal Dynamics During Infection’, October 2–5, 2005, Edinburgh, Scotland Maik J. Lehmann 1 and Freddy Frischknecht 2, * 1 Department of Virology, Hygiene Institute, University of Heidelberg Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany 2 Department of Parasitology, Hygiene Institute, University of Heidelberg Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany *Corresponding author: Freddy Frischknecht, freddy. frischknecht@med.uni-heidelberg.de Received 9 January 2006, revised and accepted for pub- lication 27 January 2006 In early 1996, Pascale Cossart and colleagues wrote a short landmark paper in Science (1) summarizing the thoughts of many researchers to announce the opening of a new field of research at the crossroads of ‘pure’ cell biology and the studies of pathogens: cellular microbio- logy. Pathogens, having coevolved with their respective hosts, so they argued, must be masters of cell biology. Thus, by studying how pathogens usurp or modify cellular functions to their own advantage we should gain insights into the basic workings of the cell and the biology of pathogens alike. There was also a glimmer of hope that these studies might provide us with rational ways to design drugs or vaccines against disease agents that kill millions of people year after year. Almost 10 years later Michael Way convened a meeting under the auspices of the British Society for Cell Biology to take stock of where part of the field was standing. The meeting, entitled ‘Signaling and cytoskeletal dynamics during infection’, made clear how much these parts of the field have advanced and how bright a future lays ahead. Host Cell Entry by Pathogens Lewis Tilney once remarked that if one wants to study a particular cellular process, one only has to find the bug that uses it. If one is interested in the uptake of particles by a cell, pathogens are clearly the masters to study, as the first step of infection involves the entry of a pathogen into a host or host cell. That different pathogens enter their respective host cells in different ways is hardly surprising, indeed it seems that every possible way has been explored (Figure 1). In the plenary lecture, Pascale Cossart (Institut Pasteur, Paris) showed that the Gram positive bacterium Listeria monocytogenes explores two main pathways during entry. The Listeria surface proteins Internalin A and B bind to distinct receptors on the host cell surface, E-cadherin and c-Met, respectively. Both events cause the internalization of the bacterium or beads coated with either Internalin A or B. Internalin A-mediated entry proceeds through the recruitment of the cytoplasmic a- and b-catenin to the E-cadherin junction. A new molecule, ARHGAP10, which regulates actin dynamics at the Golgi, was shown to bind to a-catenin and mediate the entry of bacteria in ways that have yet to be determined. Cossart speculated that ARHGAP10 might interact with Arf6 at the bacterial entry site which, via vezatin, could lead to the recruitment of myosin VIIa. These proteins have previously been shown to play a role during entry and mediate the changes in actin poly- merization needed for the ‘silent’ entry of the bacteria (2). The second pathway relies on a different set of proteins. Many proteins of the cytoskeleton machinery were shown to be involved, including the small GTPases Rac and Cdc42, N-WASP and Wave, Arp2/3, VASP family proteins and cofilin. In addition, there is recruitment of the ubiquitin ligase Cbl, which normally regulates clathrin-mediated endocytosis. It seems Listeria uses the ubiquitin-depen- dent endocytosis of c-Met for entry, as knock-down experiments with a number of proteins implicated in endo- cytosis, including clathrin and dynamin but not AP-2, diminish the efficiency of Listeria entry into cells (3). A number of interesting observations on the entry of Gram negative bacteria based on the development of a new set of tools were presented by Markus Schlumberger (ETH, Zurich) and Guy Tran van Nhieu (Institut Pasteur, Paris). Both visualized the injection of bacterial effector proteins through the type 3 secretion system of an attaching bac- terium (Figure 2B). As the simple fusion of GFP to these proteins did not result in infectious bacteria (the fusion protein being too big to be injected), Schlumberger used an indirect recognition assay. He fused GFP to InvB, a chaperone for the secreted effector SipA and transfected it into host cells. Live cell imaging showed that GFP-InvB was lighting up at bacteria–cell contact sites some Traffic 2006; 7: 479–487 # 2006 The Authors Blackwell Munksgaard doi: 10.1111/j.1600-0854.2006.00402.x 479