2010 Fiscal Year Final Research Report
Physiological functions of the Akt substrate Girdin and its family proteins and their roles in pathogenesis
| Project/Area Number |
19209013
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagoya University |
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Principal Investigator |
TAKAHASHI Masahide Nagoya University, 大学院・医学系研究科, 教授 (40183446)
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| Co-Investigator(Kenkyū-buntansha) |
ASAI Naoya 名古屋大学, 大学院・医学系研究科, 准教授 (80273233)
ENOMOTO Atsushi 名古屋大学, 大学院・医学系研究科, 特任准教授 (20432255)
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| Project Period (FY) |
2007 – 2010
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| Keywords | Girdin / Akt / アクチン結合蛋白 / 細胞運動 / がん細胞の浸潤 / 血管新生 / 神経新生 |
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| Research Abstract |
We investigated the physiological roles of Akt substrate Girdin using a variety of cell lines and gene-targeting mice. Girdin knockdown by siRNA in various cell lines including fibroblasts, cancer cells, endothelial cells and vascular smooth muscle cells, significantly impaired their migration. Impaired cell migration by Girdin knockdown was due to the impairment of lamellipodia formation at the leading edge of migrating cells, suggesting that Girdin plays a role in actin reorganization at the leading edge. In addition, analysis of Girdin knockout mice demonstrated that Girdin plays a crucial role in postnatal angiogenesis and neurogenesis. Vascular development in the retina and brain cortex in Girdin knockout mice decreased to 60-70% compared with that of wild-type mice. Girdin deficiency also leads to overextended migration and mispositioning of the dentate granule cells, resulting in profound cytoarchitectural disorganization of the dentate gyrus which is known to develop during the early postnatal period. A novel Girdin family protein, Gipie, is expressed in endothelial cells, where it interacts with GRP78, a master regulator of ER stress. Our study indicated that Gipie/GRP78 interaction protects endothelial cells against ER stree-induced apoptosis.
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[Journal Article] Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice.2011
Author(s)
Miyamoto, R., Jijiwa, M., Asai, M., Kawai, K., Ishida-Takagishi, M., Mii, S., Asai, N., Enomoto, A., Murakumo, Y., Yoshimura, A., Takahashi M.
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Journal Title
Dev.Biol. 349
Pages: 160-168
Peer Reviewed
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[Journal Article] Roles of Disrupted-in-Schizophrenia 1-interacting protein Girdin in postnatal development of the dentate gyrus.2009
Author(s)
Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., Kaneko, N., Sawamoto, K., Miyamoto, R., Jijiwa, M., Murakumo, Y., Sokabe, M., Seki, T., Kaibuchi, K., Takahashi M.
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Journal Title
Peer Reviewed
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[Journal Article] A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.2009
Author(s)
Puseenam, A., Yoshioka, Y., Nagai R, Hashimoto R, Suyari O, Itoh M, Enomoto A, Takahashi M., Yamaguchi M.
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Journal Title
Exp.Cell Res. 315
Pages: 3370-3380
Peer Reviewed
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[Journal Article] Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.2008
Author(s)
Kitamura, T., Asai, N., Enomoto, A., Maeda, K., Kato, T., Ishida, M., Jiang, P., Watanabe, T., Usukura, J., Kondo, T., Costantini, F., Murohara, T., Takahashi M.
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Journal Title
Nature Cell Biol. 10
Pages: 329-337
Peer Reviewed
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[Journal Article] An actin-binding protein Girdin regulates the motility of breast cancer cells.2008
Author(s)
Jiang, P., Enomoto, A., Jijiwa, M., Kato, T., Hasegawa, T., Ishida, M., Sato, T., Asai, N., Murakumo, Y., Takahashi M.
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Journal Title
Cancer Res. 68
Pages: 1310-1318
Peer Reviewed
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[Journal Article] Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cell.
Author(s)
.Matsushita, E., Asai, N., Enomoto, A., Kawamoto, Y., Kato, T., Mii, S., Maeda, K., Shibata, R., Hattori, S., Hagikura, M., Takahashi, k., Sokabe, M., Murakumo, Y., Murohara, T., Takahashi M.
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Journal Title
Peer Reviewed
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