RRC ID 51349
Author Kulalert W, Sadeeshkumar H, Zhang YK, Schroeder FC, Kim DH.
Title Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2α Phosphorylation in Caenorhabditis elegans.
Journal Genetics
Abstract 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 γ-subunit of eIF2, which confers insensitivity to the effects of phosphorylated eIF2α while also altering the requirement for eIF2Bγ. 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 dauer entry through bypassing the requirement for nutritionally deficient conditions. Our data suggest that the state of eIF2α phosphorylation in the ASI sensory neuron pair may modulate internal nutrient sensing and signaling pathways, with corresponding organismal effects on development and metabolism.
Volume 206(1)
Pages 251-263
Published 2017-5-1
DOI 10.1534/genetics.117.200568
PII genetics.117.200568
PMID 28292919
PMC PMC5419473
MeSH Animals Binding Sites Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Eukaryotic Initiation Factor-2 / biosynthesis Eukaryotic Initiation Factor-2 / genetics* Eukaryotic Initiation Factor-2B / biosynthesis Eukaryotic Initiation Factor-2B / genetics* Mutation Phosphorylation Protein Biosynthesis* Sensory Receptor Cells / metabolism
IF 4.015
Times Cited 2
C.elegans tm2308