Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2α Phosphorylation in
Name
Kulalert_Kim.pdf
Size
9.9 MB
Format
Adobe PDF
Checksum (MD5)
3cdaf74a27c69ebab526fd6a9ad6d97d
Author(s)
Zhang, Ying K.
Schroeder, Frank C.
Kulalert, Warakorn
Sadeeshkumar, Harini
Kim, Dennis H.
Date Issued
May 2017
Journal
Genetics
Publisher
Genetics Society of America
Citation
Kulalert, Warakorn et al. “Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2α Phosphorylation inCaenorhabditis Elegans.” Genetics 206, 1 (March 2017): 251–263 © 2017 Genetics Society of America
Version
Author's final manuscript
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. Keywords: Caenorhabditis elegans; Dauer; EIF2α; phosphorylation; sensory neurons; translational control
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1534/genetics.117.200568
