Microtubules

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.

Structure of the microtubules: Microtubules are organized in aligned protein units whose ends are designated (+) and (-) because of their direction of polymerization. The microunits of the microtubules consist of heterodimers (without their own covalent bond), each composed of a molecular building block α- (negative) and β-tubulin (positive). From this dimeric basic structure, the filamentous basic structure of the microtubules is organized with longitudinally connected subfilaments (so-called protofilaments), of which usually 13 are laterally connected to form the wall of the microtubules. A large number of protofilaments are responsible for the typical spiral structure of the microtubules (see figure) and for their hollow body structure.

Microtubule lifespan: Microtubules have an average lifespan of about 10 minutes. It is extended if the microtubules are integrated into larger structures and thus stabilized. Basically, two different populations can be defined for microtubules:

• short-lived dynamic microtubules
• and
• long-lived, stable microtubules.

Composition of the microtubules: The composition of the microtubules is subject to constant build-up and breakdown in the cell. The tubulin units are permanently built up and broken down (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, the microtubules can dissolve completely. Depletion of the supply of tubulin units is also possible.

MAPs: Microtubule-associated proteins(MAPs) enter into specific interactions with the microtubules of the cytoskeleton. They thus influence microtubule dynamics. As stabilizing factors, the proteins bind to microtubules and slow down the depolymerization of the 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 cytostatics below, see taxanes below, see vinca alkaloids below). For example, the vinca alkaloids vincristine or vinblastine block the polymerization process by binding specifically to α-tubulin, making polymerization with β-tubulin impossible. The assembly of the microtubules is suspended.

Function of microtubules: The function of microtubules is wide-ranging and multifunctional. For example, microtubules form the spindle apparatus before cell division. The chromatids are pulled to the poles of the cell (minus ends of the microtubules) via the spindle apparatus, 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). With this type of transport, speeds of 25 to 40 centimetres per day can be achieved. The transport can take place both downstream in the direction of the synapse and in the opposite 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 partly responsible is the movement of sperm. Microtubules are also actively involved in the process of phagocytosis.

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3. 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.