Dynein is a motor protein that primarily ensures the motility of cilia and flagella. Thus, it is an important intracellular component of the ciliated epithelium, male sperm, eustachian tube, and bronchi or uterine tuba. Mutation of several genes can impair dynein function.
What is dynein?
Together with myosin, kinesin, and prestin, the cytoskeletal protein dynein forms the group of motor proteins. The allosteric motor proteins are responsible for transporting loads such as cell organelles or vesicles inside cells. They belong to the intracellular proteins and can bind to a protein network thanks to their motor domain. Their tail domain has a binding site for the loads. Dynein usually forms dimers of two monomers. They bind to microtubules, which are tubular filaments made of proteins. Transport of microtubules usually occurs from the cell membrane toward the nucleus. Dynein has several subtypes. Some are found exclusively in the axonema of cilia and flagella. Dynein, along with kinesin, is a part of microtubule filaments of the cytoskeleton. Flagella and motile cilia become a motile and alignable component due to dynein. On a biomolecular basis, several genes encode dynein. For example, the genes DNAL1, DNAI1, DNAH5, and DNAH11 are among the coding genes.
Function, action, and roles
Like all motor proteins, dynein is a transporter that transports vesicles and realizes other transport and movement processes. The molecule binds to microtubules with its head region. The tail portion can interact with lipid membranes. In the head region, dynein can bind and hydrolyze adenosine triphosphate (ATP) in two domains. In this way, the molecules provide themselves with the necessary energy for transport processes. Hydrolysis corresponds to the splitting of chemical compounds by means of the addition of a water molecule. The dipole character of the H2O molecule causes the substances to split. Each dynein complex first binds a molecule to itself. Then, thanks to the previously gained energy, it runs along a microtubule. The transport is a directed transport. This is because dynein can only travel along the microtubule in the direction of the minus end. Thus, dyneins transport their cargo from the periphery of the plasma membrane to the microtubule organizing center near the nucleus. This type of transport is also called retrograde transport. The motor protein kinesin is responsible for the oppositely directed transport. Some viruses exploit the transport processes of motor proteins to reach the nucleus of cells, such as herpes simplex. Because dynein can bind to membrane lipids and microtubules at the same time, dynein connects intracellular vesicles to the cytoskeleton and performs ATP-dependent conformational changes on them by transporting protein structure to the filament minus end.
Formation, occurrence, properties, and optimal levels
Dynein is found in the cilia of the plasma membrane. At each A tubule, a cilium bears pairs of arm-like structures, also known as dynein arms, oriented toward the B tubule of the neighboring tubule. In addition to conformational changes, dynein primarily carries out the movement of cilia and flagella. Cilia, in particular, have now been attributed vital roles as they ensure the function of many organs. The occurrence of dynein in the human organism is accordingly frequent. For example, the motor protein is found in the epithelium of the uterine tube, in the bronchi or in the sperm tail. The ciliated epithelium of the lung, the eustachian tube or the mucous membrane of the paranasal sinuses also depend on dynein. Ultimately, the molecule is a crucial component for all ciliary-bearing epithelia. The formation of the motor protein begins at the biomolecular level. Here, different genes encode for the cytoskeletal protein and acquire their functions during the embryonic phase.
Diseases and disorders
Genetic defects in the coding genes for dynein give rise to the clinical picture of Kartagener syndrome. Specifically, mutations of DNAL1, DNAI1, DNAH5, and DNAH11 have been associated with the disease to date. The function of the cilium-bearing epithelia is disturbed by the mutation. Kartagener syndrome is also called primary ciliary dyskinesia and is autosomal recessive. Cilia dyskinesia corresponds to an absence or loss of function of the dynein arms.Due to this loss of function, the mobility of the cilia is restricted or non-existent. In primary ciliary dyskinesia, the clinical picture affects all cilia-occupied cells of the body. Thus, neither the cells of the bronchial epithelium, nor those of the Eustachian tube, nor those of the paranasal sinuses are still functioning adequately. The directed ciliary beat is already absent in the embryonic phase. About half of all affected persons thus suffer from positional anomalies of numerous internal organs. As a rule, a so-called situs inversus is present. Men suffer from sperm dysknesia, which is associated with infertility. Women may also be affected by infertility due to immobility of the cilia within the uterine tuba. Because of impaired mucociliary clearance, obstruction or infection of the respiratory tract occurs. Recurrent bronchitis, rhinitis or sinusitis are common symptoms. Bronchiectasis often forms as the disease progresses. The functionality of the cilia can be checked by a cilia function test. There is no causative therapy. However, at least symptoms such as retention of airway secretions can now be controlled. Abundant fluid intake, administration of a mucolytic, and inhalation of β2-sympathomimetic are among the most important treatment options.
