Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins.
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.
Wang
Hongyan
H
Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604.
Ng
Kian Hong
KH
Qian
Hongliang
H
Siderovski
David P
DP
Chia
William
W
Yu
Fengwei
F
D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009475:Neurons, Afferent / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000502:physiology
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D044387:GTP-Binding Protein beta Subunits; D020730:Guanine Nucleotide Dissociation Inhibitors; D020662:Guanine Nucleotide Exchange Factors; C405164:Pins protein, Drosophila; D016212:Transforming Growth Factor beta; C089440:gbb protein, Drosophila; C507319:ric8a protein, Drosophila; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins