Regulation of cytoskeletal dynamics by actin-monomer-binding proteins

doi:10.1016/j.tcb.2004.05.002

Trends in Cell Biology

Volume 14, Issue 7, July 2004, Pages 386-394

https://doi.org/10.1016/j.tcb.2004.05.002 Get rights and content

Abstract

The actin cytoskeleton is a vital component of several key cellular and developmental processes in eukaryotes. Many proteins that interact with filamentous and/or monomeric actin regulate the structure and dynamics of the actin cytoskeleton. Actin-filament-binding proteins control the nucleation, assembly, disassembly and crosslinking of actin filaments, whereas actin-monomer-binding proteins regulate the size, localization and dynamics of the large pool of unpolymerized actin in cells. In this article, we focus on recent advances in understanding how the six evolutionarily conserved actin-monomer-binding proteins – profilin, ADF/cofilin, twinfilin, Srv2/CAP, WASP/WAVE and verprolin/WIP – interact with actin monomers and regulate their incorporation into filament ends. We also present a model of how, together, these ubiquitous actin-monomer-binding proteins contribute to cytoskeletal dynamics and actin-dependent cellular processes.

Section snippets

Profilin

Profilin is a small (molecular weight=12–16 kD) actin-monomer-binding protein that is found in all eukaryotes. In the absence of profilin, actin-dependent processes such as cytokinesis and polarized growth fail in flies, Dictyostelium, yeasts and mammalian cells 11, 12. The key role of profilin in actin dynamics is also supported by the fact that, together with ADF/cofilin, the Arp2/3 complex and capping protein, profilin is among the crucial components of the actin-based motility of Listeria

Actin-monomer-binding protein motifs

Despite the large number of actin-monomer-binding proteins, the majority interacts with actin through relatively few actin-monomer-binding protein motifs. The six evolutionarily conserved proteins described previously interact with G-actin through three different protein motifs: the WH2 domain, the ADF-H domain and the profilin domain. In addition, the C-terminal half of Srv2/CAP binds to monomeric actin, although the location and structure of the G-actin-binding site within this region has not

Regulation of the actin-monomer pool in cells

Actin-filament structures can be divided into two categories: linear actin-filament bundles that are nucleated by formin family proteins, and branched, Arp2/3-nucleated actin-filament networks. In budding yeast, actin cables that are involved in intracellular transport are formin-induced bundles, whereas cortical actin patches that are involved in endocytosis are nucleated by Arp2/3 [80]. In mammalian cells, the situation is more complex owing to the larger number of different actin-filament

Concluding remarks

Recent studies have demonstrated that, although actin filaments alone undergo treadmilling in vitro, virtually all of the steps in the actin-treadmilling cycle are tightly regulated in cells. Actin-monomer-binding proteins control the disassembly and assembly of actin filaments, and recharge newly polymerized actin monomers by catalyzing their nucleotide exchange. However, many important questions about the regulation of the cytoplasmic actin-monomer pool remain unanswered. It will be important

Acknowledgements

We thank Kathryn Ayscough and Keith Kozminski for their comments on the manuscript, and Marie-France Carlier for communicating her unpublished data and for the coordinates of the actin–thymosin-β4 complex. Owing to space limitations, we could not cite many of the important and relevant studies in this field.

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Trends in Cell Biology

Regulation of cytoskeletal dynamics by actin-monomer-binding proteins

Abstract

Section snippets

Profilin

Actin-monomer-binding protein motifs

Regulation of the actin-monomer pool in cells

Concluding remarks

Acknowledgements

Mech. Dev.

Curr. Opin. Cell Biol.

Int. J. Biochem. Cell Biol.

J. Biol. Chem.

Cell

Biochim. Biophys. Acta

Cell

FEBS Lett.

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FEBS Lett.

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Cell

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J. Biol. Chem.

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Curr. Biol.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Mol. Biol.

Molecular mechanisms controlling actin filament dynamics in nonmuscle cells

Annu. Rev. Biophys. Biomol. Struct.

Mechanism of actin-based motility

Science

Actin-binding proteins in the Arabidopsis genome database: properties of functionally distinct plant actin-depolymerizing factors/cofilins

Philos. Trans. R. Soc. Lond. B. Biol. Sci.

MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase δ

Biochem. J.

Actin binding proteins: regulation of cytoskeletal microfilaments

Physiol. Rev.

Profilin I is essential for cell survival and cell division in early mouse development

Proc. Natl. Acad. Sci. U. S. A.

Reconstitution of actin-based motility of Listeria and Shigella using pure proteins

Nature

In vivo importance of actin nucleotide exchange catalyzed by profilin

J. Cell Biol.

Profilin binding to poly-L-proline and actin monomers along with ability to catalyze actin nucleotide exchange is required for viability of fission yeast

Mol. Biol. Cell

Arabidopsis profilins are functionally similar to yeast profilins: identification of a vascular bundle-specific profilin and a pollen-specific profilin

Plant J.

The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins

EMBO J.

The essential role of profilin in the assembly of actin for microspike formation

EMBO J.

Formins: signaling effectors for assembly and polarization of actin filaments

J. Cell Sci.

Actin depolymerizing factor (ADF/cofilin) enhances the rate of filament turnover: implication in actin-based motility

J. Cell Biol.