The making of filopodia

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Filopodia are rod-like cell surface projections filled with bundles of parallel actin filaments. They are found on a variety of cell types and have been ascribed sensory or exploratory functions. Filopodium formation is frequently associated with protrusion of sheet-like actin filament arrays called lamellipodia and membrane ruffles, but, in comparison to these structures, the molecular details underpinning the initiation and maintenance of filopodia are only just beginning to emerge. Recent advances have improved our understanding of the molecular requirements for filopodium protrusion and have yielded insights into the inter-relationships between lamellipodia and filopodia, the two ‘sub-compartments’ of the protrusive actin cytoskeleton.

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.).

References (62)

  • S. Govind et al.

    Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin

    J Cell Biol

    (2001)
  • S. Krugmann et al.

    Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex

    Curr Biol

    (2001)
  • C. Hofmann et al.

    The genetics of Pak

    J Cell Sci

    (2004)
  • P. Aspenstrom et al.

    Rho GTPases have diverse effects on the organization of the actin filament system

    Biochem J

    (2004)
  • J.E. Bear et al.

    Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility

    Cell

    (2002)
  • C. Lebrand et al.

    Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1

    Neuron

    (2004)
  • J.S. Berg et al.

    Myosin-X is an unconventional myosin that undergoes intrafilopodial motility

    Nat Cell Biol

    (2002)
  • H. Tokuo et al.

    Myosin X transports Mena/VASP to the tip of filopodia

    Biochem Biophys Res Commun

    (2004)
  • G.I. Frolenkov et al.

    Genetic insights into the morphogenesis of inner ear hair cells

    Nat Rev Genet

    (2004)
  • M. Nozumi et al.

    Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone

    J Cell Sci

    (2003)
  • H. Nakagawa et al.

    IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena

    J Cell Sci

    (2003)
  • T.M. Svitkina et al.

    Mechanism of filopodia initiation by reorganization of a dendritic network

    J Cell Biol

    (2003)
  • S. Ritzenthaler et al.

    Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons

    Nat Neurosci

    (2000)
  • S. Passey et al.

    What is in a filopodium? Starfish versus hedgehogs

    Biochem Soc Trans

    (2004)
  • R. Kozma et al.

    The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts

    Mol Cell Biol

    (1995)
  • H. Miki et al.

    Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP

    Nature

    (1998)
  • K.E. Prehoda et al.

    Integration of multiple signals through cooperative regulation of the N-WASP–Arp2/3 complex

    Science

    (2000)
  • T.M. Svitkina et al.

    Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia

    J Cell Biol

    (1999)
  • S. Lommel et al.

    Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells

    EMBO Rep

    (2001)
  • S.B. Snapper et al.

    N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility

    Nat Cell Biol

    (2001)
  • E. Robles et al.

    Src-dependent tyrosine phosphorylation at the tips of growth cone filopodia promotes extension

    J Neurosci

    (2005)
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