Role of endosomal Rab GTPases in cytokinesis.

Completion of cytokinesis requires Rab 11-dependent membrane trafficking events to deliver new membrane to the furrow and for abscission. Many Rabs have overlapping endosomal distributions, hence, we examined whether these Rabs also function in cytokinesis. Analysis of the distribution of Rabs 4, 5, 7, 8, 9, 11, 21, and 22 revealed that only Rab 11 was enriched within the furrow of cells in telophase or present within the midbody. By contrast, Rabs 4, 5, 7, 8, and 9 were mainly localised within a peri-nuclear compartment facing away from the furrow. Using RNA interference and dominant negative Rab mutants, we evaluated the role of these Rabs in furrowing and abscission. Consistent with previous work, we find that Rab 11 is intimately involved in abscission. However, we further found that depletion of Rab 4 slowed but did not prevent abscission. Depletion of any other Rab species had little effect on furrowing or abscission. These data suggest that the membrane trafficking events required for completion of cytokinesis are largely controlled by Rab 11 and not other endosomal Rab proteins, and further suggest that the relocation of Rab 11-specific cargo is an integral facet of abscission. Arf6 knockdown was without effect on cytokinesis, but when both Rab 11 and Arf6 were knocked-down, we found the furrow rapidly regressed and the cells were unable to form a stable midbody. We suggest that Rab 11 and Arf6 function synergistically in the switch from furrowing to abscission, as well as in the terminal stage of abscission.