Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Heterotrimeric G proteins mediate asymmetric division of Drosophila neuroblasts. Free Goy appears to be crucial for the generation of an asymmetric mitotic spindle and consequently daughter cells of distinct size. However, how G beta gamma is released from the inactive heterotrimer remains unclear. Here we show that Locomotion defects (Loco) interacts and colocalizes with G alpha i and, through its GoLoco motif, acts as a guanine nucleotide dissociation inhibitor (GDI) for G alpha i. Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in G beta 13F or G gamma 1 mutants, suggesting that Loco and Pins act synergistically to release free G beta gamma in neuroblasls. Furthermore, the RGS domain of Loco can also accelerate the GTPase activity of God to regulate the equilibrium between the GDP- and the GTP-bound forms of G alpha i. Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions.