The Actin Cytoskeleton of the Cell by Laura Feeley and Jeremy Keys

Background

Representations of a. G-actin and b. F-actin. The two colors in G-actin represent the inner and outer domains of the actin monomer. These refer to the relative positions of the ends of the structure when it is integrated into the F-actin helix. Each color within the helical model represents an individual G-actin which has bonded to the filament [3]

Cytoskeleton Overview

The cytoskeleton is an array of proteins in the cytoplasm which forms the structural framework of all eukaryotic cells and most prokaryotic cells. The cytoskeleton is composed of three primary components: microtubules, actin microfilaments, and intermediate filaments. Each of these components provides a specific set of functions to regulate the overall behavior of the cell. Microtubules, composed of tubulin, are straw shaped structures which are approximately 20 nm in diameter and are the largest of the cytoskeletal components. Actin filaments are the smallest of the three components and are composed of a helical strand of actin monomers averaging around 6 nm in diameter. Intermediate filaments are twisted groups of proteins which provide tensile strength to the cell and are 10-20 nm in diameter. Collectively the cytoskeleton works to control cell shape, add structural strength, produce motility, and aid in cell division.

a) Normal actin polymerization is displayed as monomers are added to the positive end of the filament. b) ARP2/3 complex causes a branching of the filament by 70 degrees and allows for more polymerization sites. c) Cofillin splits actin chains and produces a second barbed end for more polymerization [4].

Actin

Actin is the most plentiful intercellular protein in eukarotic cells, accounting for 10% of cellular protein in muscle cells and 1-5% in most non-muscle cells. Initially recognized for its role in muscle contraction, actin is a primary component of the cellular cytoskeleton and plays a key role in cell motility, cell division, and cell-surface and cell-cell interactions.

Actin exists primarily in two forms: filamentous (F-actin) and globular actin (G-actin). Under physiological conditions, as much as 99% G-actin will naturally polymerize into F-actin [2]. Actin is often classified among three isotypes: alpha-actin, beta-actin, and gamma-actin. Alpha-actin is found primarily in muscle cells, being responsible for muscle contraction along in cooperation with myosin, while beta-actin and gamma actin are regularly associated with the cytoplasm of non-muscle cells. In addition to these three isotypes, there are numerous small variations on actin structures between organisms. While there is relatively little diversity among actin's isotypes, actin can observe a broad array of behaviors due to its interactions with actin-binding proteins (ABPs). As over 150 ABPs have been identified (which accounts for 25% of cellular proteins), actin's functions within the cytoskeleton are very diverse.

Filamentous actin is a polar structure which has a negative (or sharp) end and a positive (or barbed) end. Polymerization almost entirely occurs at the positive end of the filament. This polarity is what drives forward motion of the cell. The role of actin binding proteins on polymerization also has a significant impact on how quickly a cell is able to move. Actin related protein complex 2/3 (ARP2/3) is an actin binding protein which causes a branching of the actin filament at each of its binding sites [4]. By branching the actin, a second barbed end is formed and therefore the polymerization rate may be doubled provided there is enough G-actin available. Cofillin is another actin binding protein which produces a similar effect by splitting the polymer in half, thus producing a second barbed end and increasing the polymerization rate [4].