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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.