Mitotic Spindle Assembly: The Roles of Microtubule Nucleation and Assembly

Abstract

In all eukaryotes, the assembly of a bipolar mitotic spindle requires highly ordered arrangement of microtubule arrays. This process is facilitated by the formation of new microtubules and involves many proteins that regulate microtubule organisation and dynamics. While the γ‐tubulin ring complex ( γTuRC ) determines the spatial and temporal control over the initiation of microtubule growth, recent work reveals the molecular mechanisms behind these dynamic events. Key Concepts Mitotic spindle is a macromolecular temporary machine that initially assembles in early mitosis and disappears at the end of mitosis. Mitotic spindle mainly consists of microtubules with a variety of microtubule‐associated proteins (MAPs) and motor proteins. Microtubules are assembled from α/β‐tubulin heterodimers that contact both in longitudinal and lateral directions. The MAPs and motor proteins take responsibility for regulating the growth or shrinkage of the microtubules. Microtubule nucleation occurs at microtubule‐organising centres (MTOCs). γ‐Tubulin and several other components assemble into γ‐tubulin ring complex (γTuRC) that determines when and where to nucleate the microtubule. Diffusible RanGTP gradient from chromosomes facilitates chromosome‐mediated microtubule nucleation and assembly. Microtubules may serve as nucleation sites for microtubule nucleation and assembly regulated by γTuRC and augmin protein complex. Small microtubule seed/aster formation and sorting facilitate kinetochore capture by microtubules and mitotic spindle assembly. Mitotic kinases such as cyclin‐dependent kinases, auroras and Plks regulate microtubule nucleation and assembly during mitotic spindle formation.

The microtubule-associated protein EML3 regulates mitotic spindle assembly by recruiting the Augmin complex to spindle microtubules

“…Hice1 and hDgt6 proteins form a stable heterodimer, which then assembles with other subunits into a functional subcomplex (25). In the association of Augmin with the MTs, the phosphorylation of Hice1 by Plk1 (Pololike kinase 1) is required (40). Here, we reveal that recruitment of Augmin to the MTs depends on MT-localized EML3 under the regulation of CDK1, which phosphorylates EML3 and enhances the binding of MT-localized EML3 with Augmin and ␥-TuRC.…”