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Drosophila Ric-8 regulates Gαi cortical localization to promote Gαi-dependent planar orientation of the mitotic spindle during asymmetric cell division

Abstract

Localization and activation of heterotrimeric G proteins have a crucial role during asymmetric cell division. The asymmetric division of the Drosophila sensory precursor cell (pI) is polarized along the antero-posterior axis by Frizzled signalling and, during this division, activation of Gαi depends on Partner of Inscuteable (Pins). We establish here that Ric-8, which belongs to a family of guanine nucleotide-exchange factors for Gαi, regulates cortical localization of the subunits Gαi and Gβ13F. Ric-8, Gαi and Pins are not necessary for the control of the antero-posterior orientation of the mitotic spindle during pI cell division downstream of Frizzled signalling, but they are required for maintainance of the spindle within the plane of the epithelium. On the contrary, Frizzled signalling orients the spindle along the antero-posterior axis but also tilts it along the apico-basal axis. Thus, Frizzled and heterotrimeric G-protein signalling act in opposition to ensure that the spindle aligns both in the plane of the epithelium and along the tissue polarity axis.

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Figure 1: Gαi and ric-8a are required to polarize dividing pI cells.
Figure 2: ric-8a is required for accumulation of Gαi and Gβ13F at the cell cortex.
Figure 3: ric-8a is required for cortical localization of Gαi and Gβ13F.
Figure 4: Antero-posterior orientation of the mitotic spindle is independent of Ric-8a, Pins and Gαi.
Figure 5: Ric-8a, Gαi and Pins are required to maintain the spindle in the plane of the epithelium, whereas Fz tends to tilt it along the apico-basal axis.

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Acknowledgements

We thank D. Bilder, H. Bellen, W. Chia, Y.N. Jan, J. Knoblich, F. Matsuzaki, H. Oda, M. Sémériva, D. Strutt, A. Wodarz, X. Yang, F. Yu, the Developmental Studies Hybridoma Bank and the Bloomington Stock Center for strains and antibodies. We also thank the members of the Curie Imaging facility for their help and advice with confocal microscopy. Y.B. thanks A. Morineau for encouragement and support. We thank M. Bornens, A. Echard, M. Morgan, J. Sillibourne and M. Théry for critical comments on the manuscript in preparation. This work was supported by grants from the Association pour la Recherche sur le Cancer (ARC 4726 and ARC 7744), the Fédération pour la Recherche Médicale, the CNRS, the Curie Institute and grants from the Ministry of Research (ACI program grants). N.B.D. is supported by a postdoctoral fellowship from ARC.

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Correspondence to Nicolas B. David or Yohanns Bellaïche.

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Supplementary figure S1, S2, S3 and S4 plus Supplementary table S1 and S2 (PDF 763 kb)

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David, N., Martin, C., Segalen, M. et al. Drosophila Ric-8 regulates Gαi cortical localization to promote Gαi-dependent planar orientation of the mitotic spindle during asymmetric cell division. Nat Cell Biol 7, 1083–1090 (2005). https://doi.org/10.1038/ncb1319

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