Destabilization of Microtubules

Microtubules undergo reorganization through repeated assembly and disassembly of their tubulin subunits.  Microtubules are destabilized when the rate of catastrophe, or shortening, exceeds the rate of rescue, or elongation.

Destabilization is catalyzed by MAPs  including stathmin and kinesin-13, each having a distinct mode of action.

In the cytoplasmic pool, stathmin sequesters the tubulins by binding to two tubulin heterodimers, altering the tubulin conformation and preventing its assembly on the microtubules. This results in a shift from microtubule elongation to shrinkage.

Additionally, stathmin binds to the filament tip and bends them to  sequentially remove the heterodimeric tubulin subunits.

Kinesin-13, a non-motile member of the kinesin protein family, acts as an ATP-dependent destabilizer MAP.

ATP-bound kinesin-13 binds at the tip of the microtubules and detaches the subunits by promoting the conversion of the GTP-Beta-tubulin into GDP-Beta-tubulin. This lowers the heterodimer’s affinity towards adjacent subunits in the microtubule filament, and the kinesin-13 bound-tubulin dimers are easily released.

Upon detaching from the microtubule, ATP is hydrolyzed, and the energy from the breakdown of ATP into ADP and inorganic phosphate separates the kinesin-13 from the tubulin subunit.