Just as humans travel daily, from their house to work or even from country to country and continent to continent, so do cells. Leukocytes, for example, need to travel to different parts of the body, using blood vessels as 'highways' to the tissues, to carry out essential immune functions. Once they have reached their destination, they need to cross the blood vessel wall and move into the interstitium. As discussed by S. Nourshargh, P. Hordijk and M. Sixt on page 366, leukocytes use different strategies to migrate through the endothelium and in the interstitial space. Transendothelial migration requires intercellular communication and is governed by locally presented soluble and cell-bound signals, whereas interstitial motility is thought to be largely independent of the molecular composition of the environment and to resemble amoeboid movement.

An important aspect of intercellular communication is the coordinated organization of receptors into specialized membrane microdomains. These assemble transiently as membrane receptors bind to their ligands on the apposed membrane and bring together adhesion molecules and downstream signalling components. Indeed, as discussed by B. Manz and J. Groves on page 342, recent studies have revealed a marked effect of the spatial organization of signalling molecules on their signalling outcome.

Communication between cells can also be mediated by the addition of post-translational modifications such as ubiquitin, a small molecule modifier that tags proteins to specify distinct functional outcomes and that is recognized by ubiquitin-binding domains (UBDs). The wide range of UBDs and the functional outputs of ubiquitin–UBD interactions are outlined on a free Poster by N. Crosetto, D. Komander and I. Dikic, which was produced with generous support from Millennium Pharmaceuticals.