A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.
The Akt signaling pathway is well known to regulate cell proliferation and growth. Girdin, a novel substrate of Akt, plays a crucial role in organization of the actin cytoskeleton and cell motility under the control of Akt. We here identified a novel Girdin-like protein in Drosophila (dGirdin), which has two isoforms, dGirdin PA and dGirdin PB. dGirdin shows high homology with human Girdin in the N-terminal and coiled-coil domains, while diverging at the C-terminal domain. On establishment of transgenic fly lines, featuring knockdown or overexpression of dGirdin in vivo, overexpression in the wing disc cells induced ectopic apoptosis, implying a role in directing apoptosis. Knockdown of dGirdin in the Drosophila wing imaginal disc cells resulted in reduction of cell size. Furthermore, this was enhanced by half reduction of the Akt gene dose, suggesting that Akt positively regulates dGirdin. In the wing disc, cells in which dGirdin was knocked down exhibited disruption of actin filaments. From these in vivo analyses, we conclude that dGirdin is required for actin organization and regulation of appropriate cell size under control of the Akt signaling pathway.
Puseenam
Aekkachai
A
Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan.
Yoshioka
Yasuhide
Y
Nagai
Rika
R
Hashimoto
Reina
R
Suyari
Osamu
O
Itoh
Masanobu
M
Enomoto
Atsushi
A
Takahashi
Masahide
M
Yamaguchi
Masamitsu
M
D008841:Actin Cytoskeleton; D000818:Animals; D017209:Apoptosis; D048429:Cell Size; D004330:Drosophila / Q000166:cytology*; D029721:Drosophila Proteins / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008840:Microfilament Proteins; D030781:Organisms, Genetically Modified; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins; D014921:Wings, Animal / Q000166:cytology
C502451:CCDC88A protein, human; D029721:Drosophila Proteins; C546437:Girdin protein, Drosophila; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; D051057:Proto-Oncogene Proteins c-akt