RhoGAP54D promotes cell size asymmetry and inhibits pulsatile Myosin activity in Drosophila neural stem cells

Abstract

The Actomyosin cortex is a highly dynamic part of the cytoskeleton and cells can modulate its properties. This is important for essential cellular functions including migration, cell shape control and cleavage furrow positioning during cell division. Asymmetrically dividing Drosophila neural stem cells, called neuroblasts, exhibit stereotypic patterns of Myosin dynamics along the cell cycle. Some of the Myosin dynamics manifest as flows and are important to asymmetrically position the cleavage furrow which establishes the cell size-difference between the neuroblast and its daughter cell. Myosin can be regulated by small GTPases and their GAPs and GEFs, providing spatio-temporal control. Rho kinase downstream of the small GTPase Rho regulates Myosin activity, yet the regulation and contribution of its GEFs and GAPs to asymmetric neuroblast division are not resolved. Here, we systematically analysed the localization of RhoGAPs and RhoGEFs expressed in neuroblasts and identified the ARHGAP19 homolog RhoGAP54D as a regulator of Myosin dynamics. A cytoplasmic pool of RhoGAP54D suppresses pulsatile Myosin activity during interphase and metaphase, regulated by the nucleoporin Members Only via slow nuclear import. In anaphase RhoGAP54D is recruited to the apical cortex and constitutes the trigger that initiates the directional Myosin flow that positions the cleavage furrow. This depends on PsGEF which is itself recruited downstream of Par3/Baz and Pins, linking cell polarity to RhoGAP54D activity to promote daughter cell size asymmetry during neuroblast division.