Cytokinesis requires vesicle-mediated abscission factor recruitment to the intercellular bridge

Cellular abscission is the final step of cytokinesis that leads to cleavage of the thin intercellular bridge between the two daughter cells.

Failure of cytokinesis and abscission can result in tetraploid cells, which in the next cell division might display defects in chromosome segregation and consequent aneuploidy, a common feature of cancer cells. To understand the regulation of cytokinesis and abscission is therefore of interest in the context of cancer biology.

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^{Figure 1. Vesicle-mediated recruitment of ALIX and ESCRT-III to the intercellular bridge during cytokinesis. The study shows that ALIX and ESCRT-III co-localize on vesicles that undergo directed transport along microtubules, mediated by the kinesin-1 motor protein KIF5B, to the intercellular bridge of cytokinetic cells, thereby contributing to their function in abscission (left). The work also shows that ALIX and ESCRT-III display very similar recruitment dynamics to the midbody and formation of spiral-like filaments during abscission (right), which is in line with previous work by Addi et al. (DOI: 10.1038/s41467-020-15205-z).}

The endosomal sorting complex required for transport (ESCRT)-III orchestrates abscission by forming spiral-like filaments that mediate the final membrane scission of the thin intercellular bridge. The scaffold protein ALIX and the ESCRT-I protein TSG101 coordinately recruit ESCRT-III to the midbody. However, even though the molecular mechanisms by which ALIX and ESCRT-III are recruited to the midbody are increasingly deciphered, the spatiotemporal dynamics and transport mechanisms of these proteins to the intercellular bridge have remained unclear.

In the current article, Sascha Pust in Kaisa Haglund’s project group and colleagues in Harald Stenmark’s group address how ALIX and ESCRT-III are transported to the intercellular bridge during abscission. Using a combination of super-resolution and live-cell imaging techniques, they show that ALIX and ESCRT-III co-localize on vesicles that undergo directed transport along microtubules to the intercellular bridge during abscission (Figure 1). They elucidate that the kinesin-1 motor protein KIF5B promotes transport of ALIX-positive vesicles, the recruitment of ALIX and ESCRT-III to the midbody and the accurate timing of abscission (Figure 1).

The study thus suggests that these key abscission factors can not only be sequentially recruited, but also co-transported and co-recruited to the intercellular bridge during cytokinesis (Figure 1). Altogether, the work uncovers a previously uncharacterized vesicle-mediated co-transport of ALIX and ESCRT-III to the intercellular bridge during cytokinesis, which contributes to their roles in abscission.