As microtubules are protein polymers; that assemble into dynamic structures; essential for cell division, shape, motility, and transport of intracellular cargos. Proteins that regulate microtubule function and activity have been implicated in disorders ranging from Alzheimer’s disease to cancer. By learning how microtubules work, scientists hope to find new ways to treat these diseases.
The plus and minus ends of microtubules switch between growing and shrinking; a phenomenon known as dynamic instability. But the study discovering that the distinct rate at which tubulin protein; subunits dissociate (the tubulin “off-rate”) underlies key dynamic differences between the two ends. Dynamic organization of microtubule minus ends is vital for the formation and maintenance of acentrosomal microtubule arrays.
Structures essential for cell
In vitro, both microtubule ends switch between phases of assembly and disassembly, a behavior called dynamic instability. Although minus ends grow slower, their lifetimes are similar to those of plus ends. The mechanisms underlying these distinct dynamics remain unknown. The researchers also found that a minus-end directed motor protein, the human kinesin-14 HSET; promotes minus-end stability by suppressing the minus-end tubulin off-rate; even when challenged by the destabilizing kinesin-13 MCAK motor.
The mechanisms underlying these distinct dynamics remain unknown. Here, we use an in vitro reconstitution approach to investigate minus-end dynamics. We find that minus-end lifetimes are not defined by the mean size of the protective GTP-tubulin cap. Rather, we conclude that the distinct tubulin off-rate is the primary determinant of the difference between plus- and minus-end dynamics.
Further, our results show that the minus-end–directed kinesin-14 HSET/KIFC1 suppresses tubulin off-rate to specifically suppress minus-end catastrophe. HSET maintains its protective minus-end activity even when challenged by a known microtubule depolymerase, kinesin-13 MCAK. Our results provide novel insight into the mechanisms of minus-end dynamics, essential for our understanding of microtubule minus-end regulation in cells.
But according to the study this suggesting that the regulation of both the plus and the minus microtubule ends is integrating to form the basis for the dynamic architecture of cellular microtubules. But the dynamic organization of microtubule minus ends is vital for the formation and maintenance of acentrosomal microtubule arrays.