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PERSPECTIVES
microtubule dynamics and organization emerge from a defined set of proteins through reconstitution experiments.
Jonathon Howard. One of the big questions back when I got into the microtubule business, around 1990, was how motor proteins such as kinesin and dynein useATP hydrolysis to generate force for transport along microtubules (such as axonal transport) or for cell motility (such as ciliary or flagellar motion). The interactionof kinesin with microtubules was a model system, because it was clear that only a relatively small number of kinesins mustbe capable of moving small vesicles along microtubules. A related question was how microtubule growth and shrinkage could generate force to move chromosomes during mitosis. Polymerization and depolymerization forces were very mysterious: how could you hold on to the end of a depolymerizing microtubule? How could a microtubule grow, and new tubulin subunits get in, if its end was pushing up against something? What role did the GTP cap have, and how was energy from GTP used to generate pulling or pushing forces? How did MAPs regulate growth andshrinkage?
Carsten Janke. I entered the field of microtubule research somewhat througha back door. During my Ph.D. studies,I worked on the role of the MAP tau in neurodegeneration, and in my postdoctoral work, I characterized new kinetochore protein complexes in budding yeast. This was in the late 1990s, and at the time, the field had already expanded a lot: different research communities pursued their own interests. There were many parallel advances at the time, such as the biochemical and functional dissection of the kinetochore,the understanding of the role of primary cilia as the cell antennae, and advances in the characterization of neuronal transport mediated by microtubules. Specifically regarding microtubule research, I thinka highlight of the 1990s and 2000s wasthe use of highly sophisticated, invitro reconstructions of microtubule assemblies from recombinant components, and their biophysical characterization. This allowed the definition of minimal functional units
V I E W P O I N T
Microtubules: 50years on from thediscovery of tubulin
Gary Borisy, Rebecca Heald, Jonathon Howard, Carsten Janke, AndreaMusacchio and Eva Nogales
Abstract | Next year will be the 50thanniversary of the discovery of tubulin. Tocelebrate this discovery, six leaders in the field of microtubule research reflect on key findings and technological breakthroughs...