Title: C. elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways
VOLUME: 5 ISSUE: 1
Author(s):Michelle A. Mondoux, Michael W. Krause and John A. Hanover
Affiliation:Chief, Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bldg 8 Rm B127, 8 Center Dr MSC 0850, NIH Bethesda MD 20892-0850, USA.
Abstract: Caenorhabditis elegans is perhaps the best-understood metazoan in terms of cell fate, neural connectivity, nutrient sensing, and longevity. The study of this genetically amenable model has greatly accelerated progress in understanding human aging-associated diseases, such as diabetes and neurodegeneration. The nutrient-responsive cycling of OGlcNAc on key intracellular targets may play a key, yet unappreciated, role in human disease. Unlike their mammalian counterparts, loss-of-function mutants of ogt-1 (O-GlcNAc Transferase) and oga-1 (O-GlcNAcase) are viable in C. elegans, allowing the impact of the loss of O-GlcNAc cycling to be monitored in a living organism. C. elegans forward and reverse genetics, coupled with proteomics and chemical genomics, reveal networks of interactions and signaling pathways in which O-GlcNAc cycling may participate. The results point to a key regulatory role for O-GlcNAc cycling in cellular functions as diverse as nutrient uptake and salvage, cellular signaling, and transcription. The impact of altered O-GlcNAc cycling on the organism includes many of the hallmarks of aging-associated diseases: altered metabolism, lifespan, stress resistance, and immunity.
