Desmin is a protein found as an intermediate filament in the cytoskeleton and in striated and smooth muscle. Its role is to stabilize cells and to connect muscular structures. Genetic alterations (mutations) that cause disorders in desmin synthesis are associated with various muscle diseases such as desminopathy or cardiomyopathy.
What is desmin?
Desmin is a building block of the cytoskeleton made of protein. The protein also stabilizes the fine fibrils of muscles and is found in striated and smooth muscle. Desmin filaments belong to the intermediate filaments (filamenta intermedialia), which biology divides into five different types. According to this classification, desmin belongs to type III together with vimentin, peripherin, and glial filament protein (GFAP). Findings from animal studies suggest that vimentin may be able to replace missing desmin in early developmental stages or may be able to partially take over its functions. Genes encoding desmin are located in the human genome on the second chromosome in section 219.99 to 220 Mb. Biology used to refer to desmin as skeleton because of its stabilizing function in the cytoskeleton. Scientists Lazarides and Hubbard were the first to describe it in 1976.
Anatomy and structure
Like all proteins, desmin is made up of long chains of amino acids. These biological building blocks all follow the same basic structure and differ from each other only in their specific residues. Protein synthesis links individual amino acids with peptide bonds; in this process, the sequence of the individual building blocks depends on the sequence that the genes specify through their base sequence. Desmin consists of a total of 470 amino acids. The finished peptide chain represents the primary structure of desmin, which only becomes a finished protein in its spatial shape. After the peptide chain has been produced, further bonds form spontaneously or with the help of enzymes. These bonds, also known as hydrogen bonds, either arrange the chain into a helix (alpha structure) or format it into a leaflet (beta structure). Desmin consists of longer elongated segments and helical formations. Beyond this secondary structure, the protein adopts a more complex tertiary structure, which is also significant for the subsequent function of the protein. In addition, in some cases, different folded amino acid chains join together to form a quaternary structure within which, in principle, other biomolecules can occur. Desmin exists in secondary, tertiary and quaternary structure as a homopolymer: The polymer is a structure consisting of several macromolecules. In the case of a homopolymer such as desmin, these macromolecules or monomers are exclusively parts of the same species. A single completed desmin filament has a diameter of 8-11 nm.
Function and roles
The main function of desmin is to strengthen the cytoskeleton and musculature, and it is found in smooth and striated muscle alike. In biology, the cytoskeleton is a structure within cells that consists of proteins and gives them shape and stability. In addition, the cytoskeleton participates in the transport of substances within the cell and in its movements. Unlike the bony skeleton of the human body, the cytoskeleton does not form a fixed unit, but can flexibly adapt to the needs of the cell. Transversely striated muscles also require desmin as a connector between Z-disks and myofibrils. Z-disks mark the boundaries between contiguous muscle segments (sarcomeres) in striated muscle. Attached to the Z-disks are filament-like structures composed of a complex of actin and tropomyosin. During contraction, these fibers and filaments of myosin push into each other, temporarily shortening the tissue as a whole. Smooth muscle has a different structure than striated muscle: the fibers in it do not form clearly delineated filaments and bundles with a clearly visible striated pattern in cross-section, but appear smooth and unstructured at first glance. Nevertheless, contraction takes place in a largely similar manner.Together with non-muscle smooth muscle actin filaments, desmin also performs a stabilizing function in muscle tissue by creating strengthening bonds in so-called compaction zones.
Diseases
Several muscle diseases are associated with genetic changes (mutations) that affect the desmin genes. In humans, these are located on the second chromosome. Even if such a disease is congenital, it need not manifest itself immediately in visible symptoms. Desmin mutations in many cases lead to muscular dystrophies, which is characterized by progressive deterioration of muscular tissue. The appearance of dystrophies is very heterogeneous. A more specific clinical picture is desminopathy. This is a rare hereditary disease that leads to gradual weakening of the muscles and typically does not cause symptoms until adulthood. In desminopathy, defects in the body’s production of desmin affect both the cytoskeleton of the muscle cells and the Z-disks. In addition, desmin mutations are associated with cardiomyopathy, which can also occur as part of desminopathy. Cardiomyopathy manifests as functional cardiac problems and is not always due to disorders in desmin synthesis; instead, a variety of possible causes can be considered. Typical signs of the disease include heart failure, arrhythmias, syncope, angina pectoris and embolism. Furthermore, the detection of desmin antibodies helps physicians distinguish between different tumors – for example, rhabdomyosarcomas (malignant tumors in soft tissue with a high mortality rate) and leiomyosarcomas (malignant tumors in smooth muscle).
