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Current Signal Transduction Therapy


ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

C. elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways

Author(s): Michelle A. Mondoux, Michael W. Krause and John A. Hanover

Volume 5, Issue 1, 2010

Page: [60 - 73] Pages: 14

DOI: 10.2174/157436210790226456

Price: $65


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.

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