Trends in Cell Biology
Regulation of cytoskeletal dynamics by actin-monomer-binding proteins
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Ayscough and Keith Kozminski for their comments on the manuscript, and Marie-France Carlier for communicating her unpublished data and for the coordinates of the actin–thymosin-β4 complex.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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