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

• Published in: Nature cell biology Vol. 7; no. 11; pp. 1091 - 1098
• Main Authors: Chia, William, Yu, Fengwei, Wang, Hongyan, Ng, Kian Hong, Qian, Hongliang, Siderovski, David P
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2005
• Subjects: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Cell Cycle Proteins - metabolism; Cell division; Cell Division - physiology; Cell Polarity; Control; Drosophila; Drosophila - embryology; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Embryos; G proteins; 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; Insects; Mammals; Models, Biological; Nematodes; Neurons; Neurons, Afferent - physiology; Physiological aspects; Proteins; Stem Cells - drug effects; Stem Cells - ultrastructure; Transforming Growth Factor beta - physiology; United States; Singapore
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb1317

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 Gα, 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 pI cells. Ric-8 is necessary for membrane targeting of Gαi, Pins and Gβ13F, presumably by regulating multiple Gα subunit(s). Ric-8 forms an in vivo complex with Gαi and interacts preferentially with GDP-Gαi, which is consistent with Ric-8 acting as a GEF for Gαi. Comparisons of the phenotypes of Gαi, Ric-8, Gβ13F single and Ric-8;Gβ13F double loss-of-function mutants indicate that, in NBs, Ric-8 positively regulates Gαi activity. In addition, Gβγ acts to restrict Gαi (and GoLoco proteins) to the apical cortex, where Gαi (and Pins) can mediate asymmetric spindle geometry.