Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor

Abstract

Eukaryotic translation initiation factor 5A (eIF5A), the only known protein containing the polyamine-derived amino acid hypusine, modulates protein synthesis. We show that neurotrophic and neuroprotective actions of nerve growth factor (NGF) are mediated by hypusinated eIF5A, which can account for the known roles of polyamines in cell growth and survival. NGF treatment of PC12 cells stimulates eIF5A formation. Moreover, prevention of hypusine formation by a selective inhibitor of deoxyhypusine synthase and by its depletion with RNA interference blocks the NGF-elicited augmentation of neurite outgrowth and cell survival of PC12 cells. In brain cultures, inhibition of hypusine formation also inhibits neuronal process extension.hypusine ͉ spermidine ͉ nerve growth factor ͉ arginase ͉ deoxyhypusine synthase

Single‐Cell Mass Spectrometry for Discovery Proteomics: Quantifying Translational Cell Heterogeneity in the 16‐Cell Frog (Xenopus) Embryo

“…For example, expression was higher for Vdac2 and Eif5a in D11 as well as for Tbx6r and Vtga2 in V21. In agreement, we earlier found Vdac2 to be more highly abundant in D11 cells, Eif5a plays a role in brain development and function,27 a stereotypical fate of the D11 cell type,16 and vegetal cells are known to contain more yolk platelets. Intriguingly, differential protein expression signifies that asymmetry along the animal‐vegetal (V11 vs. V21) and dorsal‐ventral (D11 vs. V11) axes of the 16‐cell embryo are already established when transcriptional asymmetry is evidenced only along the animal‐vegetal axis based on deep sequencing of the single‐blastomere transcriptomes 28…”

Involvement of eukaryotic translation initiation factor 5A (eIF5A) in skeletal muscle stem cell differentiation

“…Other studies associated eIF5A with the transport of macromolecules through nuclear pore complex (Cullen, 1992;Ruhl et al, 1993;Bevec et al, 1996;Schatz et al, 1998;Rosorius et al, 1999;Lipowsky et al, 2000;Hofmann et al, 2001) and with decay of transcripts (Zuk and Jacobson, 1998). Some observations suggest that eIF5A might play an important role in brain development and function (Sano et al, 1984;Abbruzzese, 1988;Huang et al, 2007;Luchessi et al, 2008). In spite of these observations, however, the precise function of the eIF5A remains to be elucidated.…”

uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs

“…How polyamines might affect the activity of any of these factors leading to more efficient initiation on the AUU codon of uORF-M or whether there are other non-polyamine-related conditions that produce the same effect is unknown. Although eIF5A has the essential polyamine-derived modification, hypusine, it is not established that it is involved in the initiation step of protein synthesis (32).…”