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Molecular motors and microtubule self-repair

​The microtubules are rigid but fragile biological polymers that define the cellular road network. They are crossed by molecular vehicles that transport proteins from one end of the cell to the other. Scientists have shown that this transport induces damage to the lattice of the microtubules that can quickly lead to their complete destruction. They also discovered that a self-repair mechanism allows the microtubules to resist the damages induced by this molecular transport and even be strengthened by it.

Published on 27 January 2021
These results are published in the journal Nature Materials.

Imagine if our roads could self-repair the damage caused by road traffic. No more potholes, no more cracks to repair, just the pleasure of driving on a perfect asphalt, the dream... This process of self-repair of the communication network has been highlighted on microtubules, real cellular highways, following the damage caused by molecular motors necessary for intracellular transport.
Microtubules are rigid biological polymers that travel through the cell. They are assembled from tubulin dimers. Microtubules are involved in intracellular transport. They are permanently driven by molecular motors, kinesins or dyneins, which use the energy of ATP to transport cargoes and thus ensure the transport of proteins. The microtubules, during their assembly, are mainly composed of GTP tubulin dimers, but rapidly the hydrolysis of the nucleotide into GDP will mark their aging.
In a collaboration with the University of California San Diego (UCSD), among others, the researchers were able to show that motile molecular motors can remove dimers along the microtubules. This damage can lead to the total destruction of the microtubules. This destruction of microtubules was demonstrated in an in vitro biomimetic system mimicking intracellular transport (Figure). However, in the presence of free tubulin dimer, microtubules can self-repair the damage induced by molecular motors. This self-repair mechanism was observed in vitro using green fluorescent microtubules in the presence of red tubulin dimers. The self-repair of damage induced by molecular motors appears as red dots along green microtubules.

Figure: Destruction of microtubules by molecular motors. The microtubule (green) is traversed by molecular motors (purple) in a reconstituted system in vitro. Molecular motors remove tubulin dimers from the microtubule inducing its fragmentation and depolymerization. 
Observation by evanescent wave microscopy.
© Sarah Triclin, Cytomorpholab.

This process of self-repair has several interests. First, it avoids the destruction of the microtubules travelled by the molecular motors and therefore allows the maintenance of the road on which the transport is carried out. Second, it will contribute to the rejuvenation of the microtubules. Indeed, the subunits damaged by the molecular motors are (aged) GDP tubulin dimers. During self-repair these GDP subunits will be replaced by GTP tubulin dimers. Thanks to this mechanism, the microtubules traveled by molecular motors will be damaged and self-repaired and thus rejuvenated and strengthened. Thus, this mechanism promotes transportation and can turn frequently used small roads into highways.

Self-repair and rejuvenation are processes that we would like to be able to associate with many biological functions. It is now important to study what implications these mechanisms will have on intracellular organization, to determine whether certain microtubules will preferentially be affected by these processes and thus acquire particular properties that can generate specific cellular responses.

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