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Milestone 23

Branching out

Isolation of the first actin nucleator

Nature Reviews Molecular Cell Biology volume 9, pages s20–s21 (2010)Cite this article

Laura Machesky in Tom Pollard's laboratory purified the intact Arp2/3 complex from Acanthamoeba castellanii based on its affinity for the actin-binding protein profilin, and showed that it consists of a stable assembly of seven polypeptides. Two of the subunits were actin-related proteins of the Arp2 and Arp3 subfamilies, giving the complex its name. The authors localized the complex at the leading edge of motile cells and presciently suggested that the unconventional actins dimerize to “form a cryptic nucleus for actin filament formation”. Matt Welch in Tim Mitchison's laboratory confirmed this hypothesis by showing that the Arp2/3 complex was the key factor involved in nucleating Listeria monocytogenes actin tails in in vitro motility assays.

This work paved the way for exploring the regulators of the Arp2/3 complex, many of which turned out to be effectors of Rho GTPases. In 1998, Machesky and Insall showed that a domain shared by Wiskott–Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous protein (WAVE; also known as suppressor of cyclic AMP repressor (SCAR)) binds to the Arp2/3 complex. In parallel, Ma et al. provided a direct link between signalling pathways and actin nucleation, by showing that the Rho GTPase CDC42 binds and activates proteins that stimulate actin polymerization by the Arp2/3 complex. Machesky and collaborators, followed by several other laboratories, found that WASP/WAVE proteins are nucleation-promoting factors (NPFs) for the Arp2/3 complex.

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References

ORIGINAL RESEARCH PAPERS

  1. Machesky, L. M., Atkinson, S. J., Ampe, C., Vandekerckhov, J. & Pollard, T. D. Purification of a cortical complex containing two unconventional actins from Acanthamoeba by affinity chromatography on profilin-agarose. J. Cell Biol. 127, 107–115 (1994)

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

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FURTHER READING

  1. Welch, M. D., DePace, A. H., Verma, S., Iwamatsu, A. & Mitchison, T. J. The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J. Cell Biol. 138, 375–384 (1997)

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  2. Machesky, L. M. et al. Scar, a WASp-related protein activates nucleation of actin filaments by the Arp2/3. Proc. Natl Acad. Sci. USA 96, 3739–3744 (1999)

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  3. Pruyne, D. et al. Role of formins in actin assembly: nucleation and barbed-end association. Science 297, 612–615 (2002)

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  4. Sagot, I. Rodal, A. A., Moseley, J., Goode, B. L. & Pellman, D. An actin nucleation mechanism mediated by Bni1 and profilin. Nature Cell Biol. 4, 626–631 (2002)

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  1. Senior Editor, Nature Reviews Molecular Cell Biology,

    Ekat Kritikou

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Kritikou, E. Branching out. Nat Rev Mol Cell Biol 9 (Suppl 1), s20–s21 (2010). https://doi.org/10.1038/nrm2565

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