Actin: Function & Diseases

Actin is a structural protein found in all eukaryotic cells. It participates in the assembly of the cytoskeleton and muscle.

What is actin?

Actin is a protein molecule with a very old developmental history. As a structural protein, it is present in the cytoplasm of every eukaryotic cell and in the sarcomere of all muscle fibers. Together with microtubules and intermediate filaments, it forms the cytoskeleton of every cell in the form of actin filaments. It is jointly responsible for the formation of the cell structure and the movement of molecules and cell organelles within the cell. The same applies to the cohesion of cells via tight junctions or adherens junctions. In muscle fibers, actin, together with the proteins myosin, troponin and tropomyosin, generates muscle contractions. Actin can be divided into the three functional units alpha-actin, beta-actin and gamma-actin. Alpha-actin is the structural component of muscle fibers, while beta- and gamma-actin are mainly found in the cytoplasm of cells. Actin is a highly conserved protein, occurring with very slight variations in amino acid sequence in unicellular eukaryotic cells. In humans, 10 percent of all protein molecules in muscle cells consist of actin. All other cells still contain 1 to 5 percent of this molecule in the cytoplasm.

Function, action, and tasks

Actin performs important functions in cells and muscle fibers. In the cytoplasm of the cell, as a component of the cytoskeleton, it forms a dense, three-dimensional network that holds cellular structures together. At certain points in the network, the structures reinforce each other to form membrane bulges such as microvilli, synapses or pseudopodia. Adherens junctions and tight junctions are available for cell contacts. Overall, actin thus contributes to the stability and shape of cells and tissues. In addition to stability, actin also provides transport processes within the cell. It tightly binds important structurally related transmembrane proteins so that they remain in spatial proximity. With the help of myosins (motor proteins), actin fibers also take over transport over short distances. For example, vesicles can be transported to the membrane. Longer distances are covered by the microtubules with the help of the motor proteins kinesin and dynein. Furthermore, actin also ensures cell motility. Cells must be able to migrate within the body on many occasions. This is especially true during immune reactions or wound healing, as well as during general movements or changes in the shape of cells. The movements can be based on two different processes. First, movement can be triggered by a directed polymerization reaction and second, via actin-myosin interaction. In actin-myosin interaction, actin fibers are structured as bundles of fibrils that function like traction ropes with the help of myosin. Actin filaments can form cell outgrowths in the form of pseudopodia (filopodia and lamellipodia). In addition to its many functions within the cell, actin is of course responsible for muscle contraction of both skeletal muscle and smooth muscle. These movements are also based on actin-myosin interaction. To ensure this, many actin filaments are linked to other proteins in a very orderly fashion.

Formation, occurrence, properties, and optimal values

As mentioned earlier, actin is found in all eukaryotic organisms and cells. It is an intrinsic component of the cytoplasm and provides cell stability, anchorage of structurally related proteins, short-distance transport of vesicles to the cell membrane, and cell motility. Without actin, cell survival would not be possible. There are six different actin variants, which are divided into three alpha variants, one beta variant and two gamma variants. The alpha actins are involved in the formation and contraction of muscles. Beta-actin and gamma-1-actin have great importance for the cytoskeleton in the cytoplasm. Gamma-2-actin, in turn, is responsible for smooth muscle and intestinal muscle. During synthesis, monomeric globular actin is formed first, which is also known as G-actin. The individual monomeric protein molecules in turn assemble under polymerization to form filamentous F-actin. During the polymerization process, several globular monomers combine to form a long filamentous F-actin.Both the assembly and the disassembly of the chains are very dynamic. This means that the actin scaffold can be quickly adapted to current requirements. In addition, cell movements are also ensured by this process. These reactions can be inhibited by so-called cytoskeleton inhibitors. These substances are used to inhibit either polymerizations or depolymerizations. They have medicinal significance as drugs in the context of chemotherapy.

Diseases and disorders

Because actin is an essential component of all cells, many structural changes caused by mutation lead to death of the organism. Mutations in genes encoding alpha-actins can cause muscle diseases. This is especially true for alpha-1-actin. Due to the fact that alpha-2-actin is responsible for aortic muscle, a mutation in the ACTA2 gene can cause familial thoracic aortic aneurysm. The ACTA2 gene encodes alpha-2-actin. Mutation of the ACTC1 gene for cardiac alpha-actin causes dilated cardiomyopathy. Furthermore, mutation of ACTB as the gene encoding cytoplasmic beta-actin can cause large cell and diffuse B-cell lymphoma. Some autoimmune diseases may have elevated levels of actin antibodies. In particular, this is true for autoimmune liver inflammation. This is a chronic hepatitis that leads to liver cirrhosis in the long term. Here, an antibody against smooth muscle actin is found. In terms of differential diagnosis, however, autoimmune hepatitis is not so easy to distinguish from chronic viral hepatitis. This is because antibodies against actin may also be stimulated to a lesser extent in chronic viral hepatitis.