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| Cellular functions depend on the spatial and temporal regulation of many complex biomolecular interactions. In clathrin-mediated endocytosis, a dynamic network of protein interactions is organised by the AP2 a-appendage, acting as a controlling hub. The cover illustrates the multiplicity of known protein interactions which centre around the AP2 a-appendage during the formation of clathrin-coated vesicles. The a-appendage structure is shown in the centre with direct interactions shown in green and interactions between the binding partners shown in orange. Directionality in clathrin-mediated endocytosis is generated by alterations in the preferred binding partners in response to clustering of the a-appendage. The cover illustration is based on an image generated by M.G.J. Ford, G.J.K Praefcke and H.T. McMahon, co-authors of a related article appearing on pages 4371-4383 of this issue. The McMahon group at the MRC Laboratory of Molecular Biology in Cambridge, UK, studies the molecular mechanisms of membrane curvature and budding. Visit their web site at http://www2.mrc-lmb.cam.ac.uk/groups/hmm
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