The unique contributions of Rab11 and Rab35 to the completion of cell division

Rab11 and Rab35 have been implicated in large-scale intracellular membrane trafficking during the last phases of the cell cycle. Although both proteins are associated with cytokinetic abscission, they appear to perform distinct functions and give rise to different phenotypes in dividing cells. Despite a substantial body of research on each protein individually, no study to date has systematically compared Rab11 and Rab35 in the context of cancer cell division. As a result, the extent of their interrelationship and potential compensatory mechanisms remains unclear. Our data demonstrate that Rab11a, Rab11b and Rab35 expression levels are partially interrelated. We also show that Rab11 and Rab35 contribute to mitotic progression in different ways, particularly during specific stages of the M-phase. Notably, depletion of either Rab11 or Rab35 disrupts cytokinetic abscission and correlates with aberrant F-actin accumulation at the intercellular bridge. Furthermore, overexpression of related Rab proteins with overlapping functions does not rescue the cytokinetic defects caused by Rab11 or Rab35 downregulation in cancer cells. Therefore, this study aims to deepen our understanding of how Rab11 and Rab35 orchestrate the molecular events that drive the progression from late anaphase through the completion of cytokinesis.