Abstract
Author SummarySeveral bacteria and viruses hijack the motile machinery of cells they invade to generate networks of actin filaments (comet tails) to propel themselves from one cell to another. A proper understanding of the mechanism of propulsion has so far been hampered by a lack of information about the structure of the machinery. Using electron tomography we present here the three-dimensional structure of actin comet tails propelling a baculovirus, the smallest pathogen known to recruit the actin nano-machinery. We show that baculovirus is propelled by a fishbone-like array of actin filaments constructed from subsets linked by branch junctions, with an average of four filaments pushing the virus by their fast polymerizing ends at any one time. Using a stochastic mathematical model we have simulated comet tail organization as well as the tracks adopted by baculovirus inside cells. The simulations support a model of baculovirus propulsion in which the actin filaments are continuously tethered to the virus surface as they grow, branch, and push. Since larger pathogens like Listeria, Shigella, and Vaccinia virus generate comet tails exhibiting the same general morphology and components as those of baculovirus, the basic mechanism of their propulsion is likely a scaled up version of the one described here.
Highlights
The seminal finding of Tilney and Portnoy [1] that Listeria monocytogenes exploits the actin cytoskeleton of infected cells to invade neighboring cells opened a new chapter in motile processes based on actin
Several bacteria and viruses hijack the motile machinery of cells they invade to generate networks of actin filaments to propel themselves from one cell to another
Using electron tomography we present here the three-dimensional structure of actin comet tails propelling a baculovirus, the smallest pathogen known to recruit the actin nano-machinery
Summary
The seminal finding of Tilney and Portnoy [1] that Listeria monocytogenes exploits the actin cytoskeleton of infected cells to invade neighboring cells opened a new chapter in motile processes based on actin. Major progress in understanding how L. monocytogenes uses actin to move came from the identification of the Arp2/3 complex [2] as the downstream target promoting actin polymerization [3] and from the subsequent elucidation of the minimal protein cocktail required for propulsion in vitro [4]. Essential in the in vitro motility mix was actin, the Arp2/3 complex, ADF/cofilin, an actin capping protein and an activator of the Arp2/3 complex, ActA on L. monocytogenes, or N-WASP on plastic beads [4,5]. Subsequent studies have revealed a growing list of bacterial and viral pathogens that exploit the actin-based motile machinery of infected cells by mimicking or recruiting N-WASP to activate the Arp2/3 complex [6,7] or other actin nucleators [8]. Electron microscopy of plastic-embedded, negatively stained L. monocytogenes comet tails, or critical point dried tails on ActA-coated beads [1,9,10,11] showed actin filaments more or less randomly oriented, but the high density of filaments precluded definition of their spatial organization by conventional 2D imaging
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