Microtubule nucleation for spindle assembly: one molecule at a time.

For a long time, it was unclear how the myriads of microtubules are generated in a spindle to orchestrate cell division. In recent years, many microtubule nucleation pathways that generate spindle microtubules have been identified and shed light on this question. Moreover, the γ-tubulin ring complex (γ-TuRC), once thought to be the cell's sole nucleator, is now known to work synergistically with the protein XMAP215/ch-TOG. Recent high resolution cryogenic electron microscopy structures and in vitro single molecule studies of γ-TuRC provided clues towards its mode of action. It is an emerging concept that biomolecular condensation plays a role in microtubule nucleation in the spindle. The next challenge will be to determine how γ-TuRC is targeted to the right location in the spindle at the right time and subsequently turned on to generate the spindle framework. The cell orchestrates the dance of chromosome segregation with remarkable speed and fidelity. The mitotic spindle is built from scratch after interphase through microtubule (MT) nucleation, which is dependent on the γ-tubulin ring complex (γ-TuRC), the universal MT template. Although several MT nucleation pathways build the spindle framework, the question of when and how γ-TuRC is targeted to these nucleation sites in the spindle and subsequently activated remains an active area of investigation. Recent advances facilitated the discovery of new MT nucleation effectors and their mechanisms of action. In this review, we illuminate each spindle assembly pathway and subsequently consider how the pathways are merged to build a spindle. [ABSTRACT FROM AUTHOR]