@misc{oai:ir.soken.ac.jp:00001032, author = {兼崎, 琢麿 and カネサキ, タクマ and KANESAKI, Takuma}, month = {2016-02-17}, note = {Heterotrimeric G protein signaling is involved in various pathways in animal
development. During Drosophila gastrula ion, Ga12 (Cta)mediated signaling
controls the ventral cellular movements of epithelia. Here, I show that G Protein
signaling also regulates the organization of cortical actin cytoskeleton underlining
plasma membrane in the epithelial cells. Multiple Gα subfamilies, Gα12 and
Gαi, are involved in the actin organization, but a known ligand of Gα12, Fog, is
not required. When rie-8, which is required for plasma membrane-targeting of
whole G proteins and their signaling activity, is mutated, the cell surfaces become
unstable and show blebs, and entire cellular movements in gastrulation are
delayed. The mutants for the common cofactors of the Gα's, GB13F and Gγ1,
show the similar phenotypes. Ventral cells also showed blebs like the ric-8
mutant when the cells are treated with inhibitors of actin polymerization. The
disruption of cortical actin in the mutants for G proteins is seen in all epithelial
cells, but the disorganization of the surface occurs only in the moving ventral cells.
This suggests that the organization of cortical actin seems to be required to
endure the stress, which the ventral cells receive when they move during
gastrulation.
Besides, I also show evidence that heterotrimeric G protein signaling is
involved in the control of the actin dynamics in syncytial blastderm stage. In
this stage, nuclear division is carried out with the assistance of two architectures
of actin cytoskeleton; actin caps in interphase and pseudocleavage
furrow-assembled actin network in mitosis. G protein is colocalized with the caps
and network of actin throughout this stage. In the ric-8mutant, this localization
pattern is lost and actin cytoskeleton shows abnormal morphology. Using
live-imaging technique, it is revealed that the ric-8 mutant shows the delay of the
change of actin morphology. These results suggest that G protein regulates
timing of the dynamic change of actin during mitosis, and provide new insight
into the role of G protein signaling in early embryogenesis of Drosophi7a.
In addition, here I introduce a novel mutant of ric-8 gene, ric8atx, in which
408th E is substituted to K. The ric8atx mutant embryo shows cta- or fog like
phenotype of gastrulation, which is milder than that of the ric-8 null mutant.
Consistently, the ric8atx mutation results in the Gα12-specific defect of targeting.
Although the role of Ric-8 has been inferred from the results of genetic analyses
and of some in vitro assays in past studies, the true molecular function of this
protein is stil1 unclear. The findings from the analyses of ric8atx promote
elucidating the mysterious function of Ric-8 protein in viva ., 総研大甲第1061号}, title = {Roles of Ric-8 dependent targeting of heterotrimeric G proteins in early embryogenesis of Drosophila}, year = {} }