REGULATION OF THE ACTIN CYTOSKELETON TRANSFORMATION IN THE CELL BY Arp2/3 COMPLEX. REVIEW

The cytoskeleton is formed by a network of protein filaments, including microtubules, actin filaments and intermediate filaments. Filaments permeate the entire cytoplasm; they are involved in maintaining the cell shape, they organize and anchor the organelles, they control the transport of various molecules, cell division and provide signal transduction. To implement these diverse and complex functions, the components of the cytoskeleton must be very dynamic and mobile, be able to rebuilt quickly and interact with each other. This is due to the presence of a large number of actin-binding proteins – nucleators, activators, inactivators of polymerization and depolymerization of actin filaments. This review describes the regulation of actin dynamics by the Arp2/3 complex. In the cell, this complex is in an inactive state. Its activation occurs after the interaction with activators. Activators change the conformation and spatial arrangement of the domains of the Arp2/3 complex, providing its interaction with monomeric and polymeric actin.
Activators of the Arp2/3-complex have been known for a long time and include such proteins as WASp and WAVE. All activators possess a specific VCA domain, which is responsible for their binding to the Arp2/3 complex. The structure of the complex with bound activators has been studied using various physico-chemical methods. The inactivators of the complex only recently attracted specific attention of the investigators. At present, at least five different proteins are known to inactivate the Arp2/3 complex by binding to its various subunits. Examples of inactivators are coronin, Gmf and arpin. The structure of the Arp2/3 complex with inactivators was recently published and showed that despite their binding to different subunits of the complex, all inactivators transform the Arp2/3 complex into an “open” state, moving the actin-like Arp subunits
apart from each other. Studies of the spatial organization of actin-binding proteins are necessary for understanding the patterns of interaction between them while providing the vital activity of the cell. These data can later be used in the search for new ligands to prevent metastasis of tumor cells.

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