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oai:ir.soken.ac.jp:00001032 2023-06-20T16:09:40Z 2:430:20

Roles of Ric-8 dependent targeting of heterotrimeric G proteins in early embryogenesis of Drosophila Roles of Ric-8 dependent targeting of heterotrimeric G proteins in early embryogenesis of Drosophila 兼崎, 琢麿 カネサキ, タクマ KANESAKI, Takuma 総合研究大学院大学 博士（理学） Heterotrimeric G protein signaling is involved in various pathways in animal <br />development. During Drosophila gastrula ion, Ga12 (Cta)mediated signaling <br />controls the ventral cellular movements of epithelia. Here, I show that G Protein <br />signaling also regulates the organization of cortical actin cytoskeleton underlining <br />plasma membrane in the epithelial cells. Multiple Gα subfamilies, Gα12 and <br />Gαi, are involved in the actin organization, but a known ligand of Gα12, Fog, is <br />not required. When rie-8, which is required for plasma membrane-targeting of <br />whole G proteins and their signaling activity, is mutated, the cell surfaces become <br />unstable and show blebs, and entire cellular movements in gastrulation are <br />delayed. The mutants for the common cofactors of the Gα's, GB13F and Gγ1, <br />show the similar phenotypes. Ventral cells also showed blebs like the riｃ-8 <br />mutant when the cells are treated with inhibitors of actin polymerization. The <br />disruption of cortical actin in the mutants for G proteins is seen in all epithelial <br />cells, but the disorganization of the surface occurs only in the moving ventral cells. <br />This suggests that the organization of cortical actin seems to be required to <br />endure the stress, which the ventral cells receive when they move during <br />gastrulation. <br /> Besides, I also show evidence that heterotrimeric G protein signaling is <br />involved in the control of the actin dynamics in syncytial blastderm stage. In <br />this stage, nuclear division is carried out with the assistance of two architectures <br />of actin cytoskeleton; actin caps in interphase and pseudocleavage <br />furrow-assembled actin network in mitosis. G protein is colocalized with the caps <br />and network of actin throughout this stage. In the ric-8mutant, this localization <br />pattern is lost and actin cytoskeleton shows abnormal morphology. Using <br />live-imaging technique, it is revealed that the ric-8 mutant shows the delay of the <br />change of actin morphology. These results suggest that G protein regulates <br />timing of the dynamic change of actin during mitosis, and provide new insight <br />into the role of G protein signaling in early embryogenesis of Drosophi7a. <br /> In addition, here I introduce a novel mutant of ric-8 gene, ric8^atx, in which <br />408th E is substituted to K. The ric8^atx mutant embryo shows cta- or fog like <br />phenotype of gastrulation, which is milder than that of the ric-8 null mutant. <br />Consistently, the ric8^atx mutation results in the Gα12-specific defect of targeting. <br />Although the role of Ric-8 has been inferred from the results of genetic analyses <br />and of some in vitro assays in past studies, the true molecular function of this <br />protein is stil1 unclear. The findings from the analyses of ric8^atx promote <br />elucidating the mysterious function of Ric-8 protein in viva . 総研大甲第1061号 thesis 2007-03-23 application/pdf https://ir.soken.ac.jp/record/1032/files/甲1061_要旨.pdf https://ir.soken.ac.jp/records/1032 eng