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ACTIN COMETS' TAILS ILLUMINATE COMMONALTIES BETWEEN PATHOGEN INVASION, ORGANELLAR MOTILITY, AND CELL LOCOMOTION

Tilney and Portnoy (6) first recognized the importance of unidirectional actin polymerization in promoting the cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes. They coined the phrase "actin comet's tail" to describe the microfilaments streaming behind the bacteria as they are propelled through the cytoplasm and into the tips of pseudopod projections by the rapidly polymerizing actin (top left and right images). A neighboring cell subsequently engulfs the bacteria and their associated actin tails, while these are still encapsulated in the pseudopod (lower left image). Once engulfed, the bacteria reside in the phagosome of the newly infected cell until bacterial toxins dissolve the membrane, releasing the parasite and beginning a new round of infection. Microfilament assembly is continuously nucleated on the bacterial cell surface, with the filaments kept at a short, constant length by the addition of pointed end capping proteins (4, 5). The universality of comets' tails was recognized recently when endosomes and lysosomes were seen to streak through cytoplasmic extracts propelled by the trailing filaments (2). It is now evident that Listeria activates the critical host Arp2/3 complex controlling the spatial and temporal distribution of actin polymerization (7). In uninfected cells, Arp2/3 complex is regulated by neural Wiskott-Aldrich syndrome proteins (N-WASP), and together these molecules are recognized as key factors in promoting actin-based cell locomotion, phagocytosis, and organellar motility (1, 3). In the last few years, studies using bacterial pathogen model systems and molecular analyses of Wiskott-Aldrich syndrome have converged on common factors involved in the control of actin polymerization, factors that are critical for a variety of cellular functions. Reproduced from The Journal of Cell Biology, 1989, 109: 1597-1608, by Copyright permission of the Rockefeller University Press.---Angela Wandinger-Ness

REFERENCES

1.  Novak, K. (1999). Mutant WASp stops cells in their tracks. Nat. Med. 5, 1128.

2.  Taunton, J., Rowning, B.A., Coughlin, M.L., Wu, M., Moon, R.T., Mitchison, T.J., and Larabell, C.A. (2000). Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP. J. Cell Biol. 148, 519-530.

3.  Thrasher, A.J., and Burns, S. (1999). Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation. Microsc. Res. Tech. 47, 107-113.

4.  Tilney, L.G., DeRosier, D.J., and Tilney, M.S. (1992). How Listeria exploits host cell actin to form its own cytoskeleton. I. Formation of a tail and how that tail might be involved in movement. J. Cell Biol. 118, 71-81.

5.  Tilney, L.G., DeRosier, D.J., Weber, A., and Tilney, M.S. (1992). How Listeria exploits host cell actin to form its own cytoskeleton. II. Nucleation, actin filament polarity, filament assembly, and evidence for a pointed end capper. J. Cell Biol. 118, 83-93.

6.  Tilney, L.G., and Portnoy, D.A. (1989). Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J. Cell Biol. 109, 1597-1608.

7.  Welch, M.D., Iwamatsu, A., and Mitchison, T.J. (1997). Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 385, 265-269.


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