Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins.
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 Galpha interaction partner Ric-8. Drosophila Ric-8 is a cytoplasmic protein that binds both the GDP- and GTP-bound form of the G-protein alpha-subunit Galphai. In ric-8 mutants, neither Galphai nor its associated beta-subunit Gbeta13F 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 Galpha protein concertina or the extracellular ligand foldedgastrulation. 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.
Hampoelz
Bernhard
B
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr Gasse 3-5, 1030 Vienna, Austria.
Hoeller
Oliver
O
Bowman
Sarah K
SK
Dunican
Dara
D
Knoblich
Juergen A
JA
D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000502:physiology*
D029721:Drosophila Proteins; D044387:GTP-Binding Protein beta Subunits; D020662:Guanine Nucleotide Exchange Factors; 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