Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity.
Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity.
Martell J1, Seo Y2, Bak DW1, Kingsley SF2, Tissenbaum HA3, Weerapana E4.
Author information
1Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA.
2Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
4Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA. Electronic address: eranthie@bc.edu.
Abstract
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.
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 27499530 PMCID: PMC5003114 [Available on 2017-08-18] DOI: 10.1016/j.chembiol.2016.06.015
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