Translatome Regulation in Neuronal Injury and Axon Regrowth

ENeuro
Meir RozenbaumMike Fainzilber

Abstract

Transcriptional events leading to outgrowth of neuronal axons have been intensively studied, but the role of translational regulation in this process is not well understood. Here, we use translatome analyses by ribosome pull-down and protein synthesis characterization by metabolic isotopic labeling to study nerve injury and axon outgrowth proteomes in rodent dorsal root ganglia (DRGs) and sensory neurons. We identify over 1600 gene products that are primarily translationally regulated in DRG neurons after nerve injury, many of which contain a 5'UTR cytosine-enriched regulator of translation (CERT) motif, implicating the translation initiation factor Eif4e in the injury response. We further identified approximately 200 proteins that undergo robust de novo synthesis in the initial stages of axon growth. ApoE is one of the highly synthesized proteins in neurons, and its receptor binding inhibition or knockout affects axon outgrowth. These findings provide a resource for future analyses of the role of translational regulation in neuronal injury responses and axon extension.

Citations

Apr 4, 2019·F1000Research·Andrea Tedeschi, Phillip G Popovich
Mar 11, 2020·Frontiers in Neuroscience·Alexander J DaviesSeog Bae Oh
Oct 20, 2018·Molecular Omics·Indrek Koppel, Mike Fainzilber
Jul 25, 2018·Molecular & Cellular Proteomics : MCP·Seung Joon LeeJeffery L Twiss
Nov 1, 2018·Molecular & Cellular Proteomics : MCP·Seung Joon LeeJeffery L Twiss
Apr 2, 2021·Journal of Proteome Research·Andres Di PaoloJosé Sotelo Silveira
Jan 16, 2021·Pain·Paulino Barragan-IglesiasZachary T Campbell
Aug 9, 2021·Current Opinion in Chemical Biology·Wouter van BergenMarc P Baggelaar

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Datasets Mentioned

BETA
GSE102316
GSE110374

Methods Mentioned

BETA
affinity purification
pull-downs
pull-down
RNA-seq
Protein Assay
immunoprecipitation

Software Mentioned

Bioconductor package
CBot
SILAC
Matlab
Nanostring
FV10
RiboTag
edgeR
MEME
STAR

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