-Tubulin and 
Gamma-tubulin (green) localizes to the two spindle poles during metaphase. Image courtesy of T. Stearns, Stanford University, USA.
The microtubule network — one of the core components of the cytoskeleton — is vital to a range of essential cellular processes, including intracellular transport and mitosis. Microtubule formation commences with nucleation — the onset of polymerization of 
-tubulin and 
-tubulin dimers — predominantly near the microtubule-organizing centres (MTOCs), although it can also occur freely in the cytoplasm. Yet, any further insight into the mechanisms and control of microtubule nucleation and network formation remained elusive until the discovery of 
-tubulin in 1989. This discovery provided the first hint of the possibility that divergent cytoskeleton family members are involved in polymer nucleation.
Previous work studying the filamentous fungus Aspergillus nidulans had revealed a genetic interaction between microtubule-interacting protein (mipA) and -tubulin, and had shown that mipA was required for microtubule function in vivo. Oakley and Oakley proceeded to clone and sequence the mipA gene, which yielded a great surprise: it was found to encode a third member of the tubulin superfamily, distinct from, but homologous to, -tubulin and -tubulin, which they named -tubulin. The ancient origin of -tubulin indicated that it is probably not restricted to A. nidulans, and, in fact, -tubulin from Drosophila melanogaster and humans was subsequently cloned and sequenced (see Further reading).
This discovery provided the first hint of the possibility that divergent cytoskeleton family members are involved in polymer nucleation.
Next, Oakley and colleagues set out to determine the function of this novel tubulin. Using integrative transformation, they initially created a mutation in the mipA gene of A. nidulans, termed mipAd1. This mutation was found to be lethal and recessive, causing drastic inhibition of cell division and partial blockade of nuclear migration in germlings. Both of these processes require microtubules, which prompted Oakley and colleagues to investigate further the precise effects of mipAd1 on the microtubule network. Interestingly, this mutation resulted in a substantial loss of microtubules and an almost complete absence of mitotic apparatus. Finally, immunofluorescence microscopy in wild-type hyphae revealed -tubulin to be a component of mitotic spindle bodies (SPBs), which are the MTOC equivalents in fungus and yeast. These observations fuelled their proposal that -tubulin is essential to the process of microtubule nucleation, attaching microtubules to the SPB.
Numerous subsequent studies confirmed and advanced these findings, with -tubulin now believed to be present in all eukaryotes and located at MTOCs, where it plays a central role in the nucleation of mitotic spindle microtubules. The complete mechanism of microtubule nucleation is still not fully understood.
