title: Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions.
abstract: Heterotrimeric G proteins mediate asymmetric division of Drosophila neuroblasts. Free Gbetagamma appears to be crucial for the generation of an asymmetric mitotic spindle and consequently daughter cells of distinct size. However, how Gbetagamma is released from the inactive heterotrimer remains unclear. Here we show that Locomotion defects (Loco) interacts and colocalizes with Galphai and, through its GoLoco motif, acts as a guanine nucleotide dissociation inhibitor (GDI) for Galphai. Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in Gbeta13F or Ggamma1 mutants, suggesting that Loco and Pins act synergistically to release free Gbetagamma in neuroblasts. Furthermore, the RGS domain of Loco can also accelerate the GTPase activity of Galphai to regulate the equilibrium between the GDP- and the GTP-bound forms of Galphai. Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions.
authors.affiliation: Temasek Lifesciences Laboratory and Department of Biological Sciences, National University of Singapore. fengwei@tll.org.sg
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Qian
authors.forename: Rachna
authors.initials: R
authors.lastname: Kaushik
authors.forename: Mary
authors.initials: M
authors.lastname: Bownes
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Yang
authors.forename: William
authors.initials: W
authors.lastname: Chia
mesh_terms: D000818:Animals; D004330:Drosophila / Q000166:cytology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008124:Locomotion; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020558:GTP Phosphohydrolases; D020962:Heterotrimeric GTP-Binding Proteins