Microtubules are protein filaments that have a tubular structure and, together with actin and intermediate filaments, form the cytoskeleton of eukaryotic cells. They stabilize the cell and also participate in transport and movement within the cell.
What are microtubules?
Microtubules are tubular polymers whose protein structures are about 24nm in diameter. Together with other filaments, they form the cytoskeleton that gives cells strength and shape. In addition, they also play an essential role in cell movement and are also important elements of cilia, flagella, centrioles and nuclear spindles. Microtubules are also very important in cancer therapy. Some agents that have an effect on tumor cell division are already used in the form of chemotherapeutics or cytostatics.
Anatomy and structure
Microtubules are composed of alpha and beta tubulin dimers (heterodimers). The heterodimers are the subunits of microtubules, which are also called protofilaments. The protofilaments build up the hollow body in the form of a spiral by intercalation, with only alpha-tubulin units at one end and only beta-tubulin subunits at the other end. Alpha- and beta-tubulin have the property of binding 1 molecule of GTP. At alpha-tubulin, GTP is irreversibly bound. The heterodimers are preferentially located at the plus end, therefore a microtubule grows in this direction, while the minus end forms the stable side. A microtubule is between one micrometer and several hundred micrometers long. The arrangement of microtubules is either singlet, duplet or triplet. The filaments normally originate from the microtubule organizing center, which includes, for example, the centrioles or the basal bodies. In addition, two different populations are distinguished: dynamic, short-lived microtubules and stable, long-lived microtubules. The stable microtubules constitute the scaffold of flagella, cilia and centrioles. Furthermore, long-lived microtubules are also found in the axons of neurons or in the flagella of sperm cells. There they provide flexibility, stability and mobility. Dynamic microtubules are also found where rapid remodeling is required. In addition, they ensure the distribution of chromosomes in the daughter cells. Microtubules are built up or broken down alternately, with building up or breaking down taking place mainly at the plus end. A microtubule grows until there are no longer enough heterodimers. Depolymerization then begins, causing the concentration of tubulin to rise again and renewed growth to begin. Different substances stop depolymerization or polymerization, these are used to treat diseases.
Function and tasks
Microtubules have multifunctional tasks. They influence the arrangement of chromosomes and vesicle movement, which functions like a rail system. Vesicle activity is a prerequisite for the transport of motor proteins. The transport takes place due to the proteins kinesin and dynein, which are located on the vesicle surface. Vesicles occupied by dynein are transported from the plus to the minus end, while vesicles occupied by kinesin are transported in the opposite direction. When individual microtubules assemble, complex structures are formed. These include the centrioles and the basal bodies. Centrioles are composed of nine microtubule triplets consisting of two incomplete and one complete microtubule. Basal bodies have the same structure as centrioles. They are located under the cell surface and have the function of anchoring flagella and kinocilia. Kinoceils are composed of a central microtubule pair and nine microtubule duplets. Kinoceils are found predominantly on epithelial cells and transport small particles on the surface of the cell. Cilia consist of a plasma membrane and are found on the surface of eukaryotic cells. Their center consists of stable microtubules arranged in the form of a bundle. Cilia provide for the movement of fluid across the cell surface. For example, they are used by some protozoa to collect food particles. Ser many cilia are found on epithelial cells, where they transport mucus layers containing dead cells or dust particles up to the throat so that they can subsequently be excreted.In addition, cilia create a current on the fallopian tube wall so that the oocytes can be transported through the fallopian tube. Flagella (flagella) have the same structure as kinocilia, but they are much longer and serve cell locomotion. This includes, for example, sperm locomotion and protozoan transport.
Diseases
In primary ciliary dysplasia, the kinocilia are defectively constructed and the number of dynein molecules is decreased. Primary ciliary dysplasia is an inherited disease that occurs very rarely and in which the transport mechanism that carries inhaled bacteria and particles does not function properly. As a result, the movement of the kinocilia is absent or very uncoordinated. For this reason, the dirt particles with the bronchial mucus or the secretion of the paranasal sinuses cannot be transported away properly, which leads to bronchiectasis (irreversible bronchial dilatation), to chronic bronchitis or to chronic sinusitis. If the flagellar beat of the sperm is disturbed in men, infertility occurs. In Alzheimer’s disease, altered microtubules are found in the brains of patients. In this disease, the enzyme MARK2 affects the protein tau. In normal cells, tau is bound to microtubules, stabilizing them. However, when MARK2 acts on tau, cytoskeletal instability and disruption in the cell transport system occur, which is one of the hallmarks of Alzheimer’s disease.