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Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins

Nature Cell Biology volume 7, pages 1099–1105 (2005)Cite this article

Abstract

Heterotrimeric G proteins act during signal transduction in response to extracellular ligands. They are also required for spindle orientation and cell polarity during asymmetric cell division. We show here that, in Drosophila, both functions require the Gα interaction partner Ric-8. Drosophila Ric-8 is a cytoplasmic protein that binds both the GDP- and GTP-bound form of the G-protein α-subunit Gαi. In ric-8 mutants, neither Gαi nor its associated β-subunit Gβ13F are localized at the plasma membrane, which leads to their degradation in the cytosol. During asymmetric cell division, this leads to various defects: apico–basal polarity is not maintained, mitotic spindles are misoriented and the size of the two daughter cells becomes nearly equal. ric-8 mutants also have defects in gastrulation that resemble mutants in the Gα protein concertina or the extracellular ligand folded gastrulation. Our results indicate a model in which both receptor-dependent and receptor-independent G-protein functions are executed at the plasma membrane and require the Ric-8 protein.

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Figure 1: Ric-8 is a cytosolic Gαi-binding protein.
Figure 2: ric-8 is required for gastrulation and asymmetric cell division.
Figure 3: Neuroblasts divide symmetrically in ric-8 mutants.
Figure 4: ric-8 is required for plasma-membrane localization of Gαi, Gαo and Gβ13F.
Figure 5: Biochemical analysis of Ric-8 function.

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Acknowledgements

We wish to thank J. Betschinger for comments on the manuscript; K. Afshar and P.Gonczy for sharing unpublished results; D. Dorner, M. Petronczki and M. Schaefer for generating UAS-Gβ13F, UAS-Gγ1, Myc–Gαi and Myc–GαiQL; S. Bhalerao and A. Hutterer for help with mutant analysis; and Y. N. Jan, T. Volk, the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for reagents. S.K.B. is supported by Boehringer Ingelheim Fonds. Work in J.A.K.'s lab is supported by the Austrian Academy of Sciences and the Austrian Research Fund (FWF).

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  1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3-5, Vienna, 1030, Austria

    Bernhard Hampoelz, Oliver Hoeller, Sarah K. Bowman, Dara Dunican & Juergen A. Knoblich

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Correspondence to Juergen A. Knoblich.

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Hampoelz, B., Hoeller, O., Bowman, S. et al. Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Nat Cell Biol 7, 1099–1105 (2005). https://doi.org/10.1038/ncb1318

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