Eukaryotic elongation factor 2 kinase regulates the synthesis of microtubule-related proteins in neurons

Justin W. Kenney, Maja Genheden, Kyung Mee Moon, Xuemin Wang, Leonard J. Foster, Christopher G. Proud

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Modulation of the elongation phase of protein synthesis is important for numerous physiological processes in both neurons and other cell types. Elongation is primarily regulated via eukaryotic elongation factor 2 kinase (eEF2K). However, the consequence of altering eEF2K activity on the synthesis of specific proteins is largely unknown. Using both pharmacological and genetic manipulations of eEF2K combined with two protein-labeling techniques, stable isotope labeling of amino acids in cell culture and bio-orthogonal non-canonical amino acid tagging, we identified a subset of proteins whose synthesis is sensitive to inhibition of eEF2K in murine primary cortical neurons. Gene ontology (GO) analyses indicated that processes related to microtubules are particularly sensitive to eEF2K inhibition. Our findings suggest that eEF2K likely contributes to neuronal function by regulating the synthesis of microtubule-related proteins. Modulation of the elongation phase of protein synthesis is important for numerous physiological processes in neurons. Here, using labeling of new proteins coupled with proteomic techniques in primary cortical neurons, we find that the synthesis of microtubule-related proteins is up-regulated by inhibition of elongation. This suggests that translation elongation is a key regulator of cytoskeletal dynamics in neurons. Modulation of the elongation phase of protein synthesis is important for numerous physiological processes in neurons. Here, using labeling of new proteins coupled with proteomic techniques in primary cortical neurons, we find that the synthesis of microtubule-related proteins is up-regulated by inhibition of elongation. This suggests that translation elongation is a key regulator of cytoskeletal dynamics in neurons.

Original languageEnglish
Pages (from-to)276-284
Number of pages9
JournalJournal of Neurochemistry
Volume136
Issue number2
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

  • SILAC
  • elongation
  • mass spectrometry
  • microtubules
  • primary neurons
  • translational control

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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