Microtubule-associated spindle organizing centres

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Centrosomes and chromosomes are two well characterized initiators of microtubule spindle assembly. Recent studies revealed another, less understood pathway of spindle microtubule assembly. In this pathway, new microtubules originate at the sides of already existing microtubules (Mahoney et al., 2006). An evidence of that came from the study by Mahoney et al., (2006) who observed plus ends of microtubules throughout the spindle in Drosophila cells. The microtubules appeared growing independently of centrosomes, yet they were directed towards the chromosomes. Additionally, γ -tubulin was found not only at centrosomes, but also throughout the spindle (Lajoie-Mazenc et al., 1994; Luders et al., 2006).

Nucleation of new microtubules from pre-existing spindle microtubules has been shown to be mediated by an Augmin complex (Goshima et al., 2008). Augmin was first identified in Drosophila, but it is conserved among higher eukaryotes (Goshima et al., 2008; Uehara et al., 2009; Petry et al., 2011). The complex is composed of 8 subunits HAUS1-8 (Dgt, Wac, Msd1 proteins in Drosophila) (Goshima et al., 2008; Meireles et al., 2009; Wainman et al., 2009; Uehara et al., 2009; Lawo et al., 2009). Function and stability of Augmin subunits is mutually dependent (Goshima et al., 2008; Petry et al., 2012).

Augmin has been proposed to laterally bind pre-existing spindle microtubules and recruit γ-TuRCs (Goshima and Kimura, 2010). Augmin-dependent recruitment of γ-tubulin to spindle microtubules generates new microtubules and increases density of the spindle (Goshima et al., 2008; Uehara et al., 2009; Wainman et al., 2009; Petry et al., 2011; Zhu et al., 2008). Accordingly, absence of any Augmin subunit results in decreased density of spindle microtubules. This mitotic effect in culture cells is stronger than in cells of a living organism (Goshima et al., 2008; Reschen et al., 2012).  Additionally, augmin mutant flies are viable (Meireles et al., 2009).

Microtubules branching in Augmin-dependent mechanism were shown to be at small angles with one another and to have identical polarity (Kamasaki et al., 2013; Petry et al., 2013). Therefore, another proposed function of Augmin is to increase efficiency of organizing polar orientation of nucleating microtubule.

Augmin is localized uniformly throughout the mitotic spindle. Some enrichment of Augmin has been shown on kinetochore microtubules (Goshima et al., 2008; Zhu et al., 2008). However, it is not known how the complex interacts with microtubules. In humans, Augmin binding to microtubules is regulated by Plk1 and Aurora A (Johmura et al., 2011; Tsai et al., 2011). The mechanism of microtubule nucleation dependent on Augmin is also not entirely clear. Human protein, Nedd1, has been proposed to target γ-TuRC to Augmin complex (Uehara et al., 2009).