Dicing with dogma: de-branching the lamellipodium.
Bottom Line: The primary event in the movement of a migrating eukaryotic cell is the extension of cytoplasmic sheets termed lamellipodia composed of networks of actin filaments.Lamellipodia networks are thought to arise through the branching of new filaments from the sides of old filaments, producing a dendritic array.These findings signal a reconsideration of the structural basis of protrusion and about the roles of the different actin nucleating and elongating complexes involved in the process.
Affiliation: Institute of Molecular Biotechnology, Austrian Academy of Sciences, Dr Bohr-Gasse 3, Vienna, Austria. email@example.comShow MeSH
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Mentions: The essential features of the model are depicted (Figure I) as originally proposed , with subsequent modifications to include filopodia formation from filaments generated in lamellipodia [47,57]. For simplicity, aspects of filament depolymerization at the rear of the lamellipodium, and recycling of actin monomer to the front are omitted. Steps 1-5 illustrate the sequence of events foreseen in the basic model: (1) Recruitment of the Scar/WAVE complex to the membrane via signal transduction pathways involving Rac and PIP2; (2) association of the Arp2/3 complex with the WAVE complex; (3) co-activation of the Arp2/3 complex by WAVE and simultaneous binding of Arp2/3 to the side of a “mother filament”; (4) nucleation and elongation of an actin filament branch with the free, polymerizing plus end pushing the membrane; (5) filament branches serve as “mother filaments” for nucleating new branches before being capped by capping protein. Steps 6-8 illustrate the proposed transitions of lamellipodia filaments into filopodia. In this scheme, filament branches originally nucleated on the WAVE/Arp2/3 complex (6,7) become associated at their plus ends with an elongation factor (e.g. Ena/VASP or a formin). The ends of the elongating filaments cluster, cross-link and generate a filopodium (8). It has been suggested that a formin could provide the mother filament to initiate the branched array (9) .
Affiliation: Institute of Molecular Biotechnology, Austrian Academy of Sciences, Dr Bohr-Gasse 3, Vienna, Austria. firstname.lastname@example.org