Mechanism of filopodia initiation by reorganization of a dendritic network

By T. Svitkina, E. Bulanova, O. Chaga, D. Vignjevic, S. Kojima, J. Vasiliev, Gary G. Borisy. Journal of Cell Biology, 2003

807 citations recorded by the source corpus.

Afilopodium protrudes by elongation of bundled actin filaments in its core. However, the mechanism of filopodia initiation remains unknown. Using live-cell imaging with GFP-tagged proteins and correlative electron microscopy, we performed a kinetic-structural analysis of filopodial initiation in B16F1 melanoma cells. Filopodial bundles arose not by a specific nucleation event, but by reorganization of the lamellipodial dendritic network analogous to fusion of established filopodia but occurring at the level of individual filaments. Subsets of independently nucleated lamellipodial filaments elongated and gradually associated with each other at their barbed ends, leading to formation of cone-shaped structures that we term Λ-precursors. An early marker of initiation was the gradual coalescence of GFP-vasodilator-stimulated phosphoprotein (GFP-VASP) fluorescence at the leading edge into discrete foci. The GFP-VASP foci were associated with Λ-precursors, whereas Arp2/3 was not. Subsequent recruitment of fascin to the clustered barbed ends of Λ-precursors initiated filament bundling and completed formation of the nascent filopodium. We propose a convergent elongation model of filopodia initiation, stipulating that filaments within the lamellipodial dendritic network acquire privileged status by binding a set of molecules (including VASP) to their barbed ends, which protect them from capping and mediate association of barbed ends with each other.

Subfields: Cell Biology

View Paper: https://www.semanticscholar.org/paper/232e41abdc8e5c35ea9d85e58aca9f9c1e025912

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Citations in the corpus

The many faces of actin: matching assembly factors with cellular structures (2007, background): “The lamellipodial network contains predominately dendritic branches in several instance”
The Actin Cytoskeleton and Actin-Based Motility (2018, background): “The long filaments can be bundled by fascin to produce filopodia (Svitkina et al. 2003) or buckled under the membrane and produce ruffles (Bear et al. 2002).”
EMT, the cytoskeleton, and cancer cell invasion (2009, background): “Filopodia formation is based on nonbranched, processive actin assembly, controlled by fascin, diaphanous and Ena/VASP [173, 182] (Fig.”
Regulation of actin assembly associated with protrusion and adhesion in cell migration. (2008, background): “To conciliate these data, it was proposed that the formation of filopodia was the result of a local rearrangement of the lamellipodial branched actin network generated by Arp2/3 into parallel filaments by proteins like fascin (218, 232).”
Filopodia: molecular architecture and cellular functions (2008, background): “Filopodia are often found embedded in or protruding from the lamellipodial actin networ”
Actin dynamics, architecture, and mechanics in cell motility. (2014, background): “Two nonexclusive mechanisms are generally admitted, one that requires the Arp2/3 complex and another that involves barbed end elongation enhancement proteins like formins or Ena/VASP proteins that will be discussed in the next paragraph (3, 4, 39, 115, 200, 256, 264, 276, 305, 323, 324, 345).”
Rho GTPases: biochemistry and biology. (2005, background): “Recent studies suggest that the formation of unbranched bundles of actin filaments found in filopodia originate from a branched network initiated by Cdc42 activation of Arp2/3 (Svitkina et al. 2003).”
A bottom-up approach to cell mechanics (2006, background): “Fascinating demonstrations of functionally relevant heterogeneities are provided by the formation of filopodia (finger-like extensions of the cytoplasm sent out by the cell in motion), in which the local activation of different actin-binding proteins enables the dynamic generation of highly localize”
Mechanical Integration of Actin and Adhesion Dynamics in Cell Migration (2010, background): “The molecular mechanisms mediating filopodial actin filament assembly likely involve mDia/formin and/or vasodilatorstimulated phosphoprotein (VASP) family proteins but are currently quite controversial (Faix & Rottner 2006, Gupton & Gertler 2007, Svitkina et al. 2003).”
The ARP2/3 complex: an actin nucleator comes of age (2006, background): “With regard to filopodia, it has been proposed that their bundled filament cores originate from ARP2/3-generated y-branched-filament networks in lamellipodi”
Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. (2003, background): “Recruitment of VASP was followed by subsequent recruitment of the F-actinbundling protein, fascin, and filopodia formation (Svitkina et al. 2003).”