The making of filopodia
Section snippets
Introduction and terminology
The exploration of new space during cell migration is mediated by protrusion of actin-rich organelles at the cell front, followed by their adhesion to extracellular matrices or cells and by cell body translocation. The best-characterized protrusive structure is the lamellipodium, comparable to the ‘pseudopod’ in Dictyostelium, which is built of a dense meshwork of branched or crosslinked actin filaments [1, 2]. Continuous lamellipodium protrusion and ruffling is frequently accompanied by the
Signalling to filopodium formation
As with other prominent cellular actin-based structures, such as stress fibres and membrane ruffles, several signalling pathways have been proposed to drive the protrusion of filopodia. Not surprisingly, most of them involve activation and subsequent effector binding of Rho-family GTPases [11]. The paradigm of such a signalling pathway in vertebrates is certainly Cdc42-mediated filopodium formation [6], which was most frequently proposed to be driven by direct interaction with proteins of the
The molecular hardware of filopodium protrusion
Our current understanding of the molecular mechanism of filopodium formation is still fragmentary. It appears that in many of the studied systems filopodia emerge from lamellipodia, suggesting that the lamellipodium serves as a precursor structure [5, 20•, 38]. The dendritic nucleation model of lamellipodium protrusion suggests that continuous actin assembly occurs by branching of new filaments off the sides or tips of pre-existing filaments, with the branching being mediated by the Arp2/3
Concluding remarks
In recent years we have witnessed significant progress in our understanding of the molecular regulation of protrusive cell-membrane structures like lamellipodia and filopodia. Several models for the mechanism of filopodium protrusion have been introduced. A key issue in the field is whether filopodia arise from lamellipodia or can form independently of the latter. As yet, several key modulators of actin filament dynamics have been implicated in affecting filopodium formation, including capping
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Theresia Stradal and Anika Steffen for kindly providing the EGFP-Drf3 construct and critical reading of the manuscript. This work was supported in part by the DFG (SPP1150 to K.R.).
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