BDNF-induced changes in the expression of the translation machinery in hippocampal neurons: protein levels and dendritic mRNA
BDNF-induced changes in the expression of the translation machinery in hippocampal neurons: protein levels and dendritic mRNA
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-tRNA-synthetase 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.
4536-4552
Manadas, Bruno
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Santos, Rita Ana
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Szabadfi, Krisztina
532bd7ca-32e7-486f-ba9a-bab25fea2efc
Gomes, João R.
5c6969f4-f1b4-4080-9df3-25be82f0cbbd
Garbis, Spiros D.
7067fd19-50c9-4d42-9611-f370289470bd
Fountoulakis, Michael
7918e434-8d49-49da-bd7e-45f71b6401b8
Duarte, Carlos B.
14728c58-b654-49c3-b3c9-f8073b1c66d4
8 October 2009
Manadas, Bruno
b8b5809f-b9fd-4646-a6fa-ee57e502f6a8
Santos, Rita Ana
5f12b0b7-7dbe-4fb9-8532-efd6ceb8e4d9
Szabadfi, Krisztina
532bd7ca-32e7-486f-ba9a-bab25fea2efc
Gomes, João R.
5c6969f4-f1b4-4080-9df3-25be82f0cbbd
Garbis, Spiros D.
7067fd19-50c9-4d42-9611-f370289470bd
Fountoulakis, Michael
7918e434-8d49-49da-bd7e-45f71b6401b8
Duarte, Carlos B.
14728c58-b654-49c3-b3c9-f8073b1c66d4
Manadas, Bruno, Santos, Rita Ana, Szabadfi, Krisztina, Gomes, João R., Garbis, Spiros D., Fountoulakis, Michael and Duarte, Carlos B.
(2009)
BDNF-induced changes in the expression of the translation machinery in hippocampal neurons: protein levels and dendritic mRNA.
Journal of Proteome Research, 8 (10), .
(doi:10.1021/pr900366x).
(PMID:19702335)
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-tRNA-synthetase 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.
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e-pub ahead of print date: 25 August 2009
Published date: 8 October 2009
Organisations:
Cancer Sciences
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Local EPrints ID: 339293
URI: http://eprints.soton.ac.uk/id/eprint/339293
ISSN: 1535-3893
PURE UUID: 249de873-8fe9-41bb-9f4c-a1379d532fea
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Date deposited: 28 May 2012 13:51
Last modified: 14 Mar 2024 11:13
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Author:
Bruno Manadas
Author:
Rita Ana Santos
Author:
Krisztina Szabadfi
Author:
João R. Gomes
Author:
Spiros D. Garbis
Author:
Michael Fountoulakis
Author:
Carlos B. Duarte
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