Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2{alpha} Phosphorylation in Caenorhabditis elegans [Developmental and Behavioral Genetics]

Cell-nonautonomous effects of signaling in the nervous system of animals can influence diverse aspects of organismal physiology. We previously showed that phosphorylation of Ser49 of the α-subunit of eukaryotic translation initiation factor 2 (eIF2α) in two chemosensory neurons by PEK-1/PERK promotes entry of Caenorhabditis elegans into dauer diapause. Here, we identified and characterized the molecular determinants that confer sensitivity to effects of neuronal eIF2α phosphorylation on development and physiology of C. elegans. Isolation and characterization of mutations in eif-2Ba encoding the α-subunit of eIF2B support a conserved role, previously established by studies in yeast, for eIF2Bα in providing a binding site for phosphorylated eIF2α to inhibit the exchange factor eIF2B catalytic activity that is required for translation initiation. We also identified a mutation in eif-2c, encoding the -subunit of eIF2, which confers insensitivity to the effects of phosphorylated eIF2α while also altering the requirement for eIF2B. In addition, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI pair of sensory neurons confers dramatic effects on growth, metabolism, and reproduction in adult transgenic animals, phenocopying systemic responses to starvation. Furthermore, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI neurons enhances da...

Source: Genetics - May 5, 2017 Category: Genetics & Stem Cells Authors: Kulalert, W., Sadeeshkumar, H., Zhang, Y. K., Schroeder, F. C., Kim, D. H. Tags: Developmental and Behavioral Genetics Source Type: research