Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated, at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development.
Bibliographical noteFunding Information:
We thank K. S. Cho, J. Chung, and K. Yu for fly stocks and DNA clones, and O. Puig and K. Yu for providing the anti-dFOXO antibody. We are also grateful to J. Lee and I. Jang for preliminary results on fly O-GlcNAcylation, other members of the Cho and Choe laboratories for helpful discussions, and E. Y. Kim and K. Yu for critical reading of the manuscript. This work was supported by the National Research Foundation (NRF) funded by the Korean Government (2010-0018923 to J.W.C. and 2010-0027736 to J.R.), World Class University Program (R31-2008-000-10086-0 to J.W.C. and J.R.) and Basic Research Program (2010-0008544 to K.-M.C.) through NRF of Korea funded by the Ministry of Education, Science and Technology and partly by KRF-2006-005-J04502 to J.W.C. Further partial support was received by NRF grant funded by the Korea government through the Center for Bioactive Molecular Hybrids (NO. R11-2003-019-00000-0 to K.S.K.). S.P. and S.-H.P are fellowship awardees of the Brain Korea 21 program. This work was made possible through the use of research facilities in the Yonsei Center for Biotechnology.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology