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

Hongyan Wang, Kian Hong Ng, Hongliang Qian, David P. Siderovski, William Chia, Fengwei Yu

Research output: Contribution to journalArticle

98 Scopus citations

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 Gα, RIC-8, which has recently been characterized in C. elegans and in mammals3-6. 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, Gβ acts to restrict Gαi (and GoLoco proteins) to the apical cortex, where Gαi (and Pins) can mediate asymmetric spindle geometry.

Original languageEnglish
Pages (from-to)1091-1098
Number of pages8
JournalNature Cell Biology
Volume7
Issue number11
DOIs
StatePublished - 1 Nov 2005

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