ALIX and ESC RT-I/II function as parallel ESC RT-III recruiters in cytokinetic abscission

Abstract

Cytokinetic abscission, the final stage of cell division where the two daughter cells are separated, is mediated by the endosomal sorting complex required for transport (ESC RT) machinery. The ESC RT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. How recruitment of these components is mediated during cytokinesis remains poorly understood, although the ESC RT-binding protein ALIX has been implicated. Here, we show that ESC RT-II and the ESC RT-II-binding ESC RT-III subunit CHMP6 cooperate with ESC RT-I to recruit CHMP4B, with ALIX providing a parallel recruitment arm. In contrast to CHMP4B, we find that recruitment of CHMP4C relies predominantly on ALIX. Accordingly, ALIX depletion leads to furrow regression in cells with chromosome bridges, a phenotype associated with abscission checkpoint signaling failure. Collectively, our work reveals a two-pronged recruitment of ESC RT-III to the cytokinetic bridge and implicates ALIX in abscission checkpoint signaling.