[Frontiers in Bioscience 15, 1164-1171, June 1, 2010]

[Frontiers in Bioscience 15, 1164-1171, June 1, 2010]

dGirdin a new player of Akt /PKB signaling in Drosophila melanogaster

Masamitsu Yamaguchi¹, Osamu Suyari¹, Rika Nagai¹, Masahide Takahashi²

¹Department of Applied Biology, Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan, ²Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi 466-8550, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Girdin: its in vivo role as the Akt substrate: 3.1. Identification of Girdin family proteins; 3.2. Role of Akt in cell size control; 3.3. Expression pattern of dGirdin PA and dGirdin PB; 3.4. dGirdin is necessary for viability of Drosophila; 3.5. dGirdin is required to control appropriate cell size in Drosophila wings; 3.6. dGirdin is necessary for actin filament accumulation and may function downstream of the Akt; 3.7. Role of Girdin in progression of human cancers; 3.8. Drosophila models for tumor metastasis and angiogenesis
4. Summary and perspective
5. Acknowledgements
References

1. ABSTRACT

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.