Two RhoGEF isoforms with distinct localisation control furrow position during asymmetric cell division

Cytokinesis partitions cellular content between daughter cells. It relies on the formation of an acto-myosin contractile ring, whose constriction induces the ingression of the cleavage furrow between the segregated chromatids. Rho1 GTPase and its RhoGEF (Pbl) are essential for this process. However, how Rho1 is regulated to sustain furrow ingression while maintaining correct furrow position remains poorly defined. Here, we show that during asymmetric division of Drosophila neuroblasts, Rho1 is controlled by two Pbl isoforms with distinct localisation. Spindlemidzone- and furrow-enriched Pbl-A focuses Rho1 at the furrowto sustain efficient ingression, while Pbl-B pan-plasmamembrane localization promotes the broadening of Rho1 activity and the subsequent enrichment of myosin on the entire cortex. This enlarged zone of Rho1 activity is critical to adjust furrow position, thereby preserving correct daughter cell size asymmetry. Our work highlights how the use of isoforms with distinct localisation makes an essential process more robust.

Automated summary

Cytokinesis, the process of cellular division, relies on the formation of a contractile ring to partition cellular content. Rho1 GTPase and its RhoGEF (Pbl) play essential roles in this process, but the regulation of Rho1 to maintain correct furrow position remains unclear. In this study, we found that two isoforms of Pbl, with distinct localisation, control Rho1 during asymmetric division in Drosophila neuroblasts. Pbl-A, enriched at the spindlemidzone and furrow, focuses Rho1 to sustain efficient ingression, while Pbl-B, localized on the entire cortex, promotes the broadening of Rho1 activity. This enlarged zone of Rho1 activity is critical for adjusting furrow position and preserving correct daughter cell size asymmetry. Our findings highlight the importance of using isoforms with distinct localisation to enhance the robustness of essential processes.