DefinitionThis section has been translated automatically.
Microtubules are composed of fine tubular protein structures and, together with the so-called intermediate filaments and the microfilaments, form the cytoskeleton of the eukaryotic cell. They thus ensure to a large extent the stability and functionality of the cell. The filaments usually originate from a center (at the minus end), the so-called microtubule organizing center (MTOC). Examples of this are the centrioles at the poles of the cells. Microtubules are often arranged as singlet, duplet or triplet organizing units.
General informationThis section has been translated automatically.
Structure of micro tubules: Microtubules are organized in directed protein units, the ends of which are designated (+) and (-) because of their direction of polymerization. The microunits of microtubules consist of heterodimers (without their own covalent bond) each composed of one molecular unit α- (negative) and β-tubulin (positive). From this dimeric basic structure, the basic filamentous structure of microtubules is organized with longitudinally connected subfilaments (so-called protofilaments) of which usually 13 are laterally linked, forming the wall of the microtubule. A large number of protofilaments are responsible for the typical spiral structure of microtubules (see figure) and for their hollow body structure.
Life span of micro tubules: Microtubules have an average life span of about 10 minutes. It is prolonged when the microtubules are incorporated into larger structures and thus stabilized. Basically, microtubules can thus be defined as having two distinct populations:
- short-lived dynamic microtubules
- long-lived, stable microtubules.
Composition of microtubules: The composition of microtubules is subject to constant formation and degradation in the cell. Thus, the tubulin units are permanently built up and degraded (poly- and depolymerized) at both their plus and minus ends. Build-up and degradation are equally balanced, so that a physiological equilibrium is created. If the balanced ratio shifts in favor of degradation, complete disintegration of the microtubules may occur. Also a depletion of the supply of tubulin units, is possible.
MAPs: Micro tubule-associated proteins (MAPs) interact specifically with the microtubules of the cytoskeleton. Thus, they exert an influence on microtubule dynamics. As stabilizing factors, the proteins bind to microtubules and slow down the depolymerization of tubulin subunits. Some MAPs additionally accelerate their polymerization, such as the assembly MAPs - Tau and MAP4.
Mitosis inhibitors: The assembly and degradation of microtubules can be inhibited by tubulin inhibitors (mitosis inhibitors: see below cytostatics, see below taxanes, see below vinca alkaloids). Thus, the vinca alkaloids vincristine or vinblastine block the polymerization process by specifically binding to α-tubulin, making polymerization with β-tubulin impossible. The assembly of microtubules is suspended.
Function of micro tubules: The function of microtubules is broad and multifunctional. Among other things, microtubules form the spindle apparatus before cell division. Via the spindle apparatus, chromatids are pulled to the poles of the cell (minus ends of microtubules), an important process in cell division (see mitosis inhibitors below).
Microtubules are also involved in the rapid axonal transport of the nerve cell. Here, mainly vesicles are moved along the microtubules by motor proteins(kinesin, dynein). In this type of transport, speeds of 25 to 40 centimetres per day can be achieved. Transport can occur both downstream towards the synapse and in the reverse direction from the synapse to the soma.
Microtubules also form flagella or cilia on certain cell types for the purpose of locomotion. One process for which microtubules are responsible is the locomotion of sperm. Microtubules are also actively involved in the process of phagocytosis.
LiteratureThis section has been translated automatically.
- Haider K et al (2019) Tubulin inhibitors as novel anticancer agents: an overview on patents (2013-2018). Expert Opin Ther Pat 29:623-641
- Knaur R et al (2014) Recent developments in tubulin polymerization inhibitors: An overview European Journal of Medicinal Chemistry 87: 89-124.
- Niu L et al (2019) Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity. J Biol Chem 294:18099-18108.