Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity
Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
In the nematode Caenorhabditis elegans, inactivating mutations in the insulin/IGF-1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a FOXO-family transcription factor. Downstream protein activities that directly regulate longevity during impaired insulin/IGF-1 signaling (IIS) are poorly characterized. Here, we use global cysteine-reactivity profiling to identify protein activity changes during impaired IIS. Upon confirming that cysteine reactivity is a good predictor of functionality in C. elegans, we profiled cysteine-reactivity changes between daf-2 and daf-16;daf-2 mutants, and identified 40 proteins that display a > 2-fold change. Subsequent RNAi-mediated knockdown studies revealed that lbp-3 and K02D7.1 knockdown caused significant increases in lifespan and dauer formation. The proteins encoded by these two genes, LBP-3 and K02D7.1, are implicated in intracellular fatty acid transport and purine metabolism, respectively. These studies demonstrate that cysteine-reactivity profiling can be complementary to abundance-based transcriptomic and proteomic studies, serving to identify uncharacterized mediators of C. elegans longevity.
DOI of Published Version
Cell Chem Biol. 2016 Aug 18;23(8):955-66. doi: 10.1016/j.chembiol.2016.06.015. Epub 2016 Aug 4. Link to article on publisher's site
Cell chemical biology
; Seo, Yonghak; Bak, Daniel W.; Kingsley, Samuel F.; Tissenbaum, Heidi A.; and Weerapana, Eranthie, "Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity" (2016). UMass Metabolic Network Publications. 31.