Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins

Nat Cell Biol. 2005 Nov;7(11):1091-8. doi: 10.1038/ncb1317.

Abstract

Asymmetric division of Drosophila neuroblasts (NBs) and the Caenorhabditis elegans zygote uses polarity cues provided by the Par proteins, as well as heterotrimeric G-protein-signalling that is activated by a receptor-independent mechanism mediated by GoLoco/GPR motif proteins. Another key component of this non-canonical G-protein activation mechanism is a non-receptor guanine nucleotide-exchange factor (GEF) for Galpha, RIC-8, which has recently been characterized in C. elegans and in mammals. We show here that the Drosophila Ric-8 homologue is required for asymmetric division of both NBs and pl cells. Ric-8 is necessary for membrane targeting of Galphai, Pins and Gbeta13F, presumably by regulating multiple Galpha subunit(s). Ric-8 forms an in vivo complex with Galphai and interacts preferentially with GDP-Galphai, which is consistent with Ric-8 acting as a GEF for Galphai. Comparisons of the phenotypes of Galphai, Ric-8, Gbeta13Fsingle and Ric-8;Gbeta13F double loss-of-function mutants indicate that, in NBs, Ric-8 positively regulates Gai activity. In addition, Gbetagamma acts to restrict Galphai (and GoLoco proteins) to the apical cortex, where Galphai (and Pins) can mediate asymmetric spindle geometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology*
  • Cell Polarity
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology
  • GTP-Binding Protein beta Subunits / physiology
  • Guanine Nucleotide Dissociation Inhibitors / physiology
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / physiology*
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Models, Biological
  • Neurons, Afferent / physiology
  • Stem Cells / drug effects
  • Stem Cells / ultrastructure
  • Transforming Growth Factor beta / physiology

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • GTP-Binding Protein beta Subunits
  • Guanine Nucleotide Dissociation Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Pins protein, Drosophila
  • Transforming Growth Factor beta
  • gbb protein, Drosophila
  • ric8a protein, Drosophila
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins