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Secrets of actin-based motility revealed by a bacterial pathogen

Nature Reviews Molecular Cell Biology volume 1, pages 110–119 (2000)Cite this article

Abstract

Actin-based cell motility is a complex process involving a dynamic, self-organizing cellular system. Experimental problems initially limited our understanding of this type of motility, but the use of a model system derived from a bacterial pathogen has led to a breakthrough. Now, all the molecular components necessary for dynamic actin self-organization and motility have been identified, setting the stage for future mechanistic studies.

Key Points

  • Crawling cells, such as epithelial cells, fibroblasts or neurons, have at their front a broad, flat region known as a lamellipodium. This region of the cell is filled with a dense meshwork of actin filaments and contains all of the machinery necessary for amoeboid motility. Actin assembly occurs primarily at the front of lamellipodia.

  • F-actin is also responsible for the intracellular movement of the bacterial pathogen Listeria monocytogenes. Its comet tail resembles a simplified lamellipodium, and the bacterial surface imitates the plasma membrane at the leading edge.

  • The Arp2/3 complex is localized to the leading edge of several cell types, and it is found throughout the actin comet tail. Arp2/3, which is activated by the surface protein, ActA, is responsible for the nucleation of actin polymerization at the bacterial surface.

  • Capping the growing barbed ends of older filaments (by capping protein CapZ and/or gelsolin) is one mechanism that could prevent the continuing elongation of older filaments. ActA may indirectly suppress capping close to the bacterial surface.

  • ADF/cofilin controls filament depolymerization.

  • Arp2/3 binds to the side of a pre-existing filament as it nucleates the growth of a new filament, so the meshwork forming at the front of the comet tail or the leading edge of the lamellipodium is effectively crosslinked at birth. In addition, numerous F-actin crosslinking proteins are found throughout the comet tail, including fimbrin and α-actinin.

  • L. monocytogenes motility can be reconstituted in vitro with a mixture of the following proteins: actin, Arp2/3, VASP, profilin, capping protein, ADF/cofilin and α-actinin, along with a steady supply of ATP. Of these proteins, only actin, Arp2/3, ADF/cofilin and capping protein are absolutely required for motility. VASP and profilin increase the rate of movement, and α-actinin stabilizes the tail.

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Figure 1: A rapidly moving cell; a keratocyte from the skin of a fish.
Figure 2: Movement of Listeria monocytogenes in an infected host cell.
Figure 3: Reconstitution of Listeria monocytogenes motility in a cytoplasmic extract.
Figure 4: Diagram of the molecular components required for actin-based motility of Listeria monocytogenes.
Figure 5: Functions of similar proteins in the lamellipodium.

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Acknowledgements

We thank Rachael Ream for digital time-lapse used to make Figure 1 and Movie 1. We would like to apologize to those researchers whose work could not be cited due to space limitations. J.A.T. is supported by grants from the National Institutes of Health and a Fellowship in Science and Engineering from the David and Lucile Packard Foundation.

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  1. Department of Biochemistry, Stanford University School of Medicine, 279 Campus Drive West, Stanford, 94305-5307, California, USA

    Lisa A. Cameron, Paula A. Giardini, Frederick S. Soo & Julie A. Theriot

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  1. Lisa A. Cameron
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  2. Paula A. Giardini
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  3. Frederick S. Soo
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  4. Julie A. Theriot
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Correspondence to Julie A. Theriot.

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ENCYCLOPEDIA OF LIFE SCIENCES

Actin and actin filaments

Glossary

AMOEBOID MOTILITY

A distinctive form of cell crawling typified by Amoeba proteus, which involves extension of pseudopodia and cytoplasmic streaming.

FIBROBLAST

Common cell type found in connective tissue in many parts of the body, which secretes an extracellular matrix rich in collagen and other macromolecules and connects cell layers.

KERATOCYTE

A small, motile cell type found in the epidermis of fish and amphibians.

LEADING EDGE

The thin margin of a lamellipodium spanning the area of the cell from the plasma membrane to about 1 μm back into the lamellipodium.

GROWTH CONE

Motile tip of the axon or dendrite of a growing nerve cell, which spreads out into a large cone-shaped appendage.

BROWNIAN RATCHET MODEL

A proposed model for actin-based motility in which actin filaments are thought to flex away from the bacterial surface to allow addition of monomer at the end of the filament. When the filament flexes back, it is one subunit longer and pushes the bacterium forward that distance.

BULK ELASTIC MODEL

A proposed model for actin-based motility, which treats the actin comet tail as a cohesive elastic gel that responds elastically to deformation. This indicates that the energy from actin polymerization may be stored as elastic energy in the actin gel to produce force that propels the bacterium forward.

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Cameron, L., Giardini, P., Soo, F. et al. Secrets of actin-based motility revealed by a bacterial pathogen. Nat Rev Mol Cell Biol 1, 110–119 (2000). https://doi.org/10.1038/35040061

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