Fascins represent small and extremely compact protein molecules that interact with actin filaments. In doing so, they bundle the actin chains, preventing their further cross-linking. Fascins further serve as markers in cancer diagnosis.
What is fascin?
Fascins are proteins that regulate the activity of actin filaments. Their role is to package actin filaments so that they are parallel and rigidly linked at the binding sites. Binding to the actin chains occurs by phosphorylation. For this purpose, they have two binding sites and form bundles of actin filaments, each ten nanometers apart. The fascins themselves are very small and compact molecules. Their weight is about 55 to 58 kilodaltons. They play a major role in the movement of actin filaments and thus of cells. Mainly in the actin-rich cell protrusions there is a lot of Fascin. These cell protrusions are also known as filopodia. Filopodia are known as the so-called false feet of radiolarians, which can also move with their help. But all eukaryotic cells also have these protrusions, so they can interact with other cells as well as serve for their locomotion. In general, there are three different forms of fascins, which are also encoded by different genes. The so-called Fascin 1 (FSCN 1) is mainly found in neurons. But it is also present in other cells in varying concentrations. Fascin 2 (FSCH 2) is produced in the retina of the eyes, and Fascin 3 (FSCN 3) is present exclusively in the testes.
Function, effects, and roles
The most important function of Fascin is to stabilize actin filaments by bundling them. Actin filaments cross-link less, contributing to the movement of cell organelles within the cell and the cell itself. Expression of Fascin occurs in all body cells. However, it is different for different cell types. There are cells that exhibit greater motility than others. For example, immune cells often need to get to their target site quickly when a focus of infection develops in a particular region of the body. The activity of actin fibers is well illustrated by the example of macrophages. When the macrophages (scavenger cells) reach the infectious invaders, they enclose them. In doing so, they form filopodia, which enclose the corresponding bacteria or foreign proteins. This allows them to incorporate them and dissolve them within the cell. The concentrations of fascins are higher the more mobile the cell has to be. The less fascin present, the more interconnected the actin filaments. This leads to more stationary cells.
Formation, occurrence, properties, and optimal values
Fascins are companion proteins of actin filaments. As mentioned earlier, they provide bundling of actin chains, thereby packaging them. This results in bundles of parallel actin filaments that lose the ability to cross-link further as a result of the packaging. Actin consists of chains of protein molecules, which are the main mass of the cytoskeleton. With the help of the cytoskeleton, cells can move around. If the actin filaments were not bundled together, they would become interconnected and restrict cell movement. An actin filament consists of a double helix of two actin chains. Fascin surrounds a bundle of actin filaments and binds them tightly at two contact sites. These contact sites are formed by phosphorylation. In phosphorylation, a phosphate group from ATP binds to a hydroxyl group of an amino acid. In the case of fascins, this is serine. The phosphates thus link the fascin molecule to the actin molecule. However, with the restriction of cross-linking, the active mobility of the actin filaments (motility) along the chain is promoted. This is accomplished by the constant degradation of the actin chain on one side with simultaneous accumulation of amino acids on the other side. This process also takes place only with the help of phosphorylation with the participation of ATP and ADP. These processes thus generate an active movement of the actin fibers. First, the cell protrusions (filopodia) are formed, which then ensure the active locomotion of the cells.Thus, by stabilizing actin filaments with Fascin and inhibiting their cross-linking, actin fiber motility is promoted
Diseases and disorders
It has also been found that the concentration of Fascin is increased in many malignant tumor cells. The resulting increased motility of these cells increases the risk of metastasis. The corresponding cells thus invade other tissues more easily and form new tumors (metastases) there. How this process actually occurs is still the subject of research. However, it is known that the filopodia play a major role in these cancer cells and that the actin fibers there are stabilized by Fascin. Thus, Fascin can be used as a tumor marker for the diagnosis of malignant neoplasms. However, an elevated concentration of Fascin does not automatically mean that cancer can be diagnosed. This finding is only an indication of a possible metastatic tumor. This is because elevated Fascin levels are not specific for tumors. The concentration of Fascins can also be elevated in other diseases. This is especially true for diseases in which there is increased production of immune cells. Immune cells must be very mobile in order to be quickly present in any place of the organism. A good example of this is infection with the Epstein-Barr virus. In this case, B lymphocytes, which contain a particularly large amount of Fascin, are formed to an increased extent.
