Research Paper Volume 2, Issue 10 pp 678—690

Intracellular protein glycosylation modulates insulin mediated lifespan in C. elegans

Mohammad M. Rahman1, , Olga Stuchlick2, , Enas G. El-Karim2, , Ryan Stuart2, , Edward T. Kipreos3, , Lance Wells2, ,

  • 1 Department of Genetics, University of Georgia, Athens, GA 30602, USA
  • 2 Department of Biochemistry & Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
  • 3 Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA

Received: October 1, 2010       Accepted: October 13, 2010       Published: October 14, 2010
How to Cite

Copyright: © 2010 Rahman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a regulatory, nuclear and cytoplasmic post-translational glycosylation of proteins associated with age-related diseases such as Alzheimer's, Parkinson's, and type II diabetes. Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems. In C. elegans, attenuation of the insulin-like signal transduction pathway increases adult lifespan of the nematode. We demonstrate that the O-GlcNAc cycling enzymes OGT and OGA, which add and remove O-GlcNAc respectively, modulate lifespan in C. elegans. Median adult lifespan is increased in an oga-1 deletion strain while median adult life span is decreased upon ogt-1 deletion. The O-GlcNAc-mediated effect on nematode lifespan is dependent on the FoxO transcription factor DAF-16. DAF-16 is a key factor in the insulin-like signal transduction pathway to regulate reproductive development, lifespan, stress tolerance, and dauer formation in C. elegans. Our data indicates that O-GlcNAc cycling selectively influences only a subset of DAF-16 mediated phenotypes, including lifespan and oxidative stress resistance. We performed an affinity purification of O-GlcNAc-modified proteins and observed that a high percentage of these proteins are regulated by insulin signaling and/or impact insulin pathway functional outcomes, suggesting that the O-GlcNAc modification may control downstream effectors to modulate insulin pathway mediated cellular processes.


O-GlcNAc: O-linked b-N-acetylglucosamine; OGT: O-GlcNAc transferase; OGA: O-GlcNAcase (neutral b-Nacetylglucosaminidase); PI3K: phosphatidylinositol-3-OH kinase.

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