Virginia Ribeiro de Andrade
Lauréat 2022

Summary of the work

Cytokinesis is the last step of cell division releasing the two daughter cells.

While in cytokinesis, the daughter cells remain connected by an intercellular bridge at the center of which the midbody recruits the ESCRT scission machinery.

The physical cut of the intercellular bridge – abscission – is driven by the ESCRT machinery at the at abscission sites, on the side of the midbody.

Interestingly, during cytokinesis the intercellular bridge experiences pulling forces, which delay abscission by preventing the assembly of the ESCRT scission machinery. Abscission is thus triggered by tension release, but how the intercellular bridge tension is controlled is unknown.

Our results reveal that caveolae, which are known to control membrane tension upon mechanical stress in interphase
cells, are located at the midbody, at the abscission site and at the intercellular bridge/cell interface in dividing cells.

Functionally, the depletion of caveolae gives rise to binucleated cells (failed abscission), and delays both abscission and the ESCRT-III recruitment to the abscission site during cytokinesis impairing abscission. This is the consequence of a 2-fold increase of intercellular bridge tension measured by laser ablation.

The tension increase is associated with a local increase in myosin II activity at the intercellular bridge/cell interface since inhibition of myosin II in caveolae depleted cells restores tension and timed abscission.

We thus propose that caveolae buffer membrane tension and limit contractility at the intercellular bridge to promote ESCRT-III assembly and cytokinetic abscission.

Altogether, this work reveals an unexpected connection between caveolae and the ESCRT machinery and the first role of caveolae in cell division.