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.
Manadas
Bruno
B
Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, Coimbra, Portugal.
Santos
Ana Rita
AR
Szabadfi
Krisztina
K
Gomes
João R
JR
Garbis
Spiros D
SD
Fountoulakis
Michael
M
Duarte
Carlos B
CB
D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016000:Cluster Analysis; D003712:Dendrites / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000378:metabolism*; D007553:Isotope Labeling; D008954:Models, Biological; D010445:Peptide Elongation Factors / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D014176:Protein Biosynthesis; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D058570:TOR Serine-Threonine Kinases
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D010445:Peptide Elongation Factors; D020543:Proteome; D012333:RNA, Messenger; D017853:Phosphotransferases (Alcohol Group Acceptor); D058570:TOR Serine-Threonine Kinases; D000604:Amino Acyl-tRNA Synthetases