TY - JOUR
T1 - Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins
AU - Wang, Hongyan
AU - Ng, Kian Hong
AU - Qian, Hongliang
AU - Siderovski, David P.
AU - Chia, William
AU - Yu, Fengwei
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=28844482414&partnerID=8YFLogxK
U2 - 10.1038/ncb1317
DO - 10.1038/ncb1317
M3 - Article
C2 - 16228012
AN - SCOPUS:28844482414
SN - 1465-7392
VL - 7
SP - 1091
EP - 1098
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 11
ER -