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Filopodia: molecular architecture and cellular functions

Nature Reviews Molecular Cell Biology volume 9, pages 446–454 (2008)Cite this article

Key Points

  • Filopodia are thin (diameter 0.1–0.3 μm) finger-like, actin-rich structures often found protruding from the lamellipodial actin network.

  • Filopodia are involved in numerous cellular processes, including cell migration, wound healing, adhesion to the extracellular matrix, guidance towards chemoattractants, neuronal growth-cone pathfinding and embryonic development.

  • The small GTPases CDC42 and RIF induce filopodia formation in cells. RIF activates actin polymerization through Dia2 formin. CDC42 might regulate filopodia formation by activating actin-filament nucleation through WASP/N-WASP and membrane deformation through IRSp53.

  • During filopodia formation, actin filaments are protected from capping and their barbed ends are clustered together by so-called tip-complex proteins, which include ENA/VASPs, Dia2 formin and myosin-X.

  • Two models for the mechanism of filopodia formation have been presented. In the so-called 'convergent elongation model' the filopodial actin filaments are derived from the ARP2/3-nucleated lamellipodial actin network, whereas an alternative model proposes that actin filaments in filopodia are nucleated at filopodial tips by formins. In this review we present a working model for filopodia formation that combines the 'convergent elongation model' and the 'de novo nucleation model'.

Abstract

Filopodia are thin, actin-rich plasma-membrane protrusions that function as antennae for cells to probe their environment. Consequently, filopodia have an important role in cell migration, neurite outgrowth and wound healing and serve as precursors for dendritic spines in neurons. The initiation and elongation of filopodia depend on the precisely regulated polymerization, convergence and crosslinking of actin filaments. The increased understanding of the functions of various actin-associated proteins during the initiation and elongation of filopodia has provided new information on the mechanisms of filopodia formation in distinct cell types.

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Figure 1: Cell migration is dependent on different actin filament structures.
Figure 2: Examples of different types of filopodia.
Figure 3: A working model for filopodia formation.

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Acknowledgements

The authors thank P. Hotulainen and J. Saarikangas for comments on the manuscript. We apologize to the people whose original articles could not be referred to due to space limitations.

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Authors and Affiliations

  1. Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Pieta K. Mattila

  2. Institute of Biotechnology, PO BOX 56, University of Helsinki, 00014, Finland

    Pieta K. Mattila & Pekka Lappalainen

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  1. Pieta K. Mattila
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  2. Pekka Lappalainen
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Correspondence to Pekka Lappalainen.

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DATABASES

Interpro

BAR

IMD

FURTHER INFORMATION

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Glossary

Lamellipodium

A cellular protrusion that is composed of a branched F-actin meshwork with, typically, 70° angles between the filaments. It results from ARP2/3 complex-mediated filament nucleation and branching. Branching frequency is highest when in close proximity to the plasma membrane, resulting in short filaments pushing against the membrane.

Barbed end

Actin filaments are polar structures. Based on the arrowhead pattern created when myosin binds actin filaments, the rapidly growing filament end is called the barbed end and the slowly growing end is called the pointed end.

Stress fibre

A contractile structure that is composed of antiparallel arrays of actin filaments associated with myosin II bundles. Stress fibres provide the contractile force that contributes to cell morphogenesis and migration.

Retrograde flow

The phenomenon whereby the speed of actin polymerization is typically faster than the velocity of cell protrusions, which leads to the sliding of actin filaments backwards with respect to the substratum.

Microspike

A short filopodium that is almost completely embedded in the cell cortex or leading edge.

Focal adhesion

A flat, elongated structure that forms cell–substrate adhesions. Focal adhesions are composed of a large number of signalling and adhesion molecules and they are associated with the ends of actin stress fibres in a wide variety of cultured adherent cells.

Adherens junction

A specialized intercellular junction of the plasma membrane, in which cadherin molecules of adjacent cells interact in a Ca2+-dependent manner. Actin filaments are linked to this structure through catenins, which are located underneath the junction.

Tectum

The midbrain roof is a retinorecipient region, referred to as the optic tectum in lower vertebrates and the superior colliculus in mammals.

I-BAR domain

A lipid-binding and deforming protein domain, which is also known as an insulin-receptor substrate p53 (IRSp53)/missing-in-metastasis (MIM) (IM)-domain.

Capping activity

Many actin-binding proteins (for example, gelsolin, EPS8, twinfilin and tropomodulin) bind to filament ends where they inhibit actin-monomer association and/or dissociation and therefore display capping activity. Uncapping activity occurs when a protein is capable of removing a capping protein from the filament end, whereas anti-capping activity occurs if a protein protects filament ends from capping proteins.

PH domain

(Pleckstrin homology). A small signal transduction domain that binds phosphatidylinositol phosphates.

SH3 domain

A small globular protein domain that interacts with Pro-rich peptides and is found in many signalling and cytoskeletal proteins.

WH2 domain

A small actin-monomer-binding protein domain that was originally identified from WASP-family proteins.

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Mattila, P., Lappalainen, P. Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol 9, 446–454 (2008). https://doi.org/10.1038/nrm2406

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