dGirdin a new player of Akt /PKB signaling in Drosophila Melanogaster.
A novel substrate of Akt/PKB designated as Girdin (griders of actin filaments) has been identified in mammals and characterized as an actin-binding protein. A Girdin-like protein has been identified in Drosophila, which has two isoforms, dGirdin PA and dGirdin PB. Knockdown of dGirdin in the Drosophila wing imaginal disc cells resulted in reduction of cell size and this was enhanced by half reduction of the Akt gene dose. Furthermore the dGirdin-knockdown wing disc cells exhibited severe 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. Human Girdin plays important roles in cancer progression and angiogenesis. Therefore Girdin and its interacting proteins could be potential pharmaceutical targets for cancer therapies and tumor angiogenesis. Possible use of the Drosophila Girdin model in understanding the mechanisms of cancer progression and in developing preventive and therapeutic strategies will be discussed.
Yamaguchi
Masamitsu
M
Department of Applied Biology, Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan. myamaguc@kit.ac.jp
Suyari
Osamu
O
Nagai
Rika
R
Takahashi
Masahide
M
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
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