BDNF-induced changes in the expression of the translation machinery in hippocampal neurons: Protein levels and dendritic mRNA

Bruno Manadas, Ana Rita Santos, K. Szabadfi, João R. Gomes, Spiros D. Garbis, Michael Fountoulakis, Carlos B. Duarte

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BDNF plays a key role in neuronal development, in short- and long-term changes in synaptic activity, and in neuronal survival. These effects are mediated, to a great extent, by changes in protein synthesis. We conducted a gel-based proteome profiling of the long-term (12 h) effects of BDNF in cultured hippocampal neurons. BDNF changed the abundance of proteins involved in (i) Nucleobase, nucleoside, nucleotide and nucleic acid metabolism, (ii) protein metabolism, (iii) carbohydrate metabolism, (iv) regulators of apoptosis, and (v) regulators of cell proliferation. A large majority of the identified proteins involved in translation activity were upregulated, but not all changes in the protein content were correlated with alterations in the corresponding mRNA. The upregulation of Seryl-aminoacyl-tRNAsynthetase and Eef2 was sensitive to the mTOR inhibitor rapamycin, as determined by Western blot. Since the mRNAs for proteins involved in translation represent a large fraction of the diversity of dendritic mRNAs, we investigated the effect of BDNF on the distribution of the transcripts in the soma versus neurite compartments. The increase in mRNA for proteins of the translation machinery in the soma was differentially coupled with the upregulation of neurite transcripts. BDNF also downregulated specific mRNAs in neurite compartments suggesting that the neurotrophin may act by regulating mRNA stability and thereby affecting the dendritic protein content.

Original languageEnglish
Pages (from-to)4536-4552
Number of pages17
JournalJournal of Proteome Research
Volume8
Issue number10
DOIs
Publication statusPublished - 2009

Fingerprint

Brain-Derived Neurotrophic Factor
Neurons
Machinery
Messenger RNA
Neurites
Proteins
Protein Biosynthesis
Carisoprodol
Nucleic Acids, Nucleotides, and Nucleosides
Up-Regulation
RNA Stability
Nerve Growth Factors
Carbohydrate Metabolism
Sirolimus
Proteome
Cell proliferation
Metabolism
Down-Regulation
Western Blotting
Gels

Keywords

  • BDNF
  • Dendritic mRNA
  • mTOR pathway
  • Translation machinery

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

BDNF-induced changes in the expression of the translation machinery in hippocampal neurons : Protein levels and dendritic mRNA. / Manadas, Bruno; Santos, Ana Rita; Szabadfi, K.; Gomes, João R.; Garbis, Spiros D.; Fountoulakis, Michael; Duarte, Carlos B.

In: Journal of Proteome Research, Vol. 8, No. 10, 2009, p. 4536-4552.

Research output: Contribution to journalArticle

Manadas, Bruno ; Santos, Ana Rita ; Szabadfi, K. ; Gomes, João R. ; Garbis, Spiros D. ; Fountoulakis, Michael ; Duarte, Carlos B. / BDNF-induced changes in the expression of the translation machinery in hippocampal neurons : Protein levels and dendritic mRNA. In: Journal of Proteome Research. 2009 ; Vol. 8, No. 10. pp. 4536-4552.
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