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Pushing with actin: from cells to pathogens.

J Victor Small1

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Summary
This summary is machine-generated.

Cellular movement and pathogen invasion rely on actin polymerization. Electron tomography revealed the structure of actin branch junctions and how viruses like baculovirus use branched actin networks for propulsion.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Structural Biology

Background:

  • Actin polymerization drives essential cellular processes like lamellipodia formation for cell movement.
  • Pathogens utilize host cell actin machinery for invasion and dissemination, forming actin comet tails.
  • Understanding the structural basis of actin network formation is crucial for cell motility and infection dynamics.

Purpose of the Study:

  • To elucidate the in situ structure of actin branch junctions within lamellipodia using electron tomography.
  • To investigate the mechanism of actin network formation and remodeling during lamellipodia protrusion and inhibition.
  • To analyze the structure of actin comet tails generated by pathogens, such as baculovirus, for propulsion.

Main Methods:

  • High-resolution electron tomography (ET) of negatively stained cytoskeletons for actin filament structure.
  • Cryo-electron tomography (cryo-ET) for preserving 3D morphology of actin networks.
  • Correlated live-cell imaging combined with ET for dynamic analysis of actin network remodeling.

Main Results:

  • A 2.9 nm resolution model of actin branch junctions was generated, closely fitting the actin-related protein 2/3 (Arp2/3)-actin complex structure.
  • Dynamic ET revealed how actin networks are assembled and remodeled during lamellipodia initiation and inhibition.
  • Baculovirus was shown to generate a fishbone-like array of branched actin filaments for propulsion, with limited filaments actively pushing.

Conclusions:

  • Electron tomography provides critical insights into the 3D structure and function of actin networks in cellular processes and pathogen motility.
  • The Arp2/3 complex is integral to the formation of branched actin junctions observed in lamellipodia.
  • Pathogen propulsion via actin comet tails involves specific, ordered arrangements of branched actin filaments.