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Comments on William Mair et al. (2009) International Worm Meeting "The role of CRTC in worm longevity." (0)
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William Mair, Ianessa Morantte, Katherine Butler, Reuben Shaw, & Andrew Dillin (2009). The role of CRTC in worm longevity presented in International Worm Meeting. Unpublished information; cite only with author permission.
Mammalian CRTC2 is a coactivator of the transcription factor cAMP Responsive Binding Protein (CREB), which is involved in diverse biological processes from memory to gluconeogenesis and fat storage. CRTC2 is a target of the nutrient responsive AMP-activated protein kinase (AMPK), which phosphorylates CRTC2, resulting in its cytoplasmic translocation and inactivation. Conversely, dephosphorylation by the phosphatase Calcineurin leads to nuclear localization of CRTC2. In C. elegans, gain of function of AMPK (aak-2), and loss of function of Calcineurin (tax-6), have been shown to extend lifespan. Here we show that the sole worm CRTC orthologue is regulated via a mechanism similar to that seen in mammals that depends upon AMPK family kinases and tax-6. Furthermore, adult-onset reduction of both CREB and CRTC in worms extends lifespan, suggesting that perturbations to AMPK and Calcineurin may prolong life in part through down-regulation of CRTC/CREB target genes.