Urge to merge erects filopodia

Urge to merge erects filopodia rawling cells often produce both broad, flat lamellipodia and long, thin filopodia. Once formed, both structures appear to use an actin-treadmilling mechanism to extend themselves. During treadmilling, lamellipodia continuously nucleate new filaments, but filopodia continue to use the same filaments. So how does a cell form a filopodium in the first place? Svitkina et al., page 409, address this question with a detailed kinetic and structural analysis, presenting a novel model that should help to guide future work in the field. Using GFP-tagged versions of the Arp2/3, VASP, and fascin proteins and innovative electron microscopy techniques, the authors examined the molecular dynamics of filopodium initiation in mouse melanoma cells. Rather than forming a distinct nucleation complex, Arp2/3 seems to lay the groundwork for filopodium birth by producing a normal lamellipodial actin array. Conical structures, termed ⌳-precursors, then rise up from this array. VASP gradually coalesces from a broad distribution along the lamellipodial edge into defined spots at the tips of the ⌳-precursors. Fascin then abruptly appears at the ⌳-precursor vertex before filopodia grow from these structures. The data suggest that, in a normal dendritic actin network in the lamellipodium, the elongating barbed ends of certain actin filaments bind to a set of molecules that protect them from capping C Anthrax toxin takes charge acterial toxin proteins are generally thought to enter eukaryotic cells by passive hitchhiking, binding to a convenient receptor that is constitutively B internalized by endocy-tosis to ensure their delivery to the cytoplasm. But on page 321, Abrami et al. show that, at least in the case of anthrax, the toxin precisely choreographs its uptake by hijacking a specific endocytic pathway. The work suggests a possible strategy for treating anthrax infections and also highlights a connection between raft-mediated and clathrin-dependent endocytosis, two pathways that were once considered to be mutually exclusive. Bacillus anthracis produces a toxin with three subunits. After binding to the and mediate their association with other elongating barbed ends. When these privileged filaments collide, they merge to form the conical ⌳-precursors, and their tip complexes then recruit or activate the bundling protein fascin, allowing filament cross-linking and the growth of long, strong actin bundles characteristic of filopodia. This model also implies that microspikes, and retraction fibers—filopodium-like structures seen in some migrating cells—arise by a similar mechanism and are inter-convertible with filopodia. In separate work, the authors have developed an in …