Dual regulation of translation initiation and peptide chain elongation during BDNF-induced LTP in vivo:: evidence for compartment-specific translation control

被引:73
作者
Kanhema, Tambudzai
Dagestad, Grethe
Panja, Debabrata
Tiron, Adrian
Messaoudi, Elhoucine
Havik, Bjarte
Ying, Shui-Wang
Nairn, Angus C.
Sonenberg, Nahum
Bramham, Clive R.
机构
[1] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway
[2] Univ Bergen, Bergen Mental Hlth Res Ctr, N-5009 Bergen, Norway
[3] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
[4] McGill Univ, Dept Biochem, Montreal, PQ H3A 2T5, Canada
关键词
dentate gyrus; hippocampus; neurotrophic factors; synaptic plasticity; translation control;
D O I
10.1111/j.1471-4159.2006.04158.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein synthesis underlying activity-dependent synaptic plasticity is controlled at the level of mRNA translation. We examined the dynamics and spatial regulation of two key translation factors, eukaryotic initiation factor 4E (eIF4E) and elongation factor-2 (eEF2), during long-term potentiation (LTP) induced by local infusion of brain-derived neurotrophic factor (BDNF) into the dentate gyrus of anesthetized rats. BDNF-induced LTP led to rapid, transient phosphorylation of eIF4E and eEF2, and enhanced expression of eIF4E protein in dentate gyrus homogenates. Infusion of the extracellular signal-regulated kinase (ERK) inhibitor U0126 blocked BDNF-LTP and modulation of the translation factor activity and expression. Quantitative immunohistochemical analysis revealed enhanced staining of phospho-eIF4E and total eIF4E in dentate granule cells. The in vitro synaptodendrosome preparation was used to isolate the synaptic effects of BDNF in the dentate gyrus. BDNF treatment of synaptodendrosomes elicited rapid, transient phosphorylation of eIF4E paralleled by enhanced expression of alpha-calcium/calmodulin-dependent protein kinase II. In contrast, BDNF had no effect on eEF2 phosphorylation state in synaptodendrosomes. The results demonstrate rapid ERK-dependent regulation of the initiation and elongation steps of protein synthesis during BDNF-LTP in vivo. Furthermore, the results suggest a compartment-specific regulation in which initiation is selectively enhanced by BDNF at synapses, while both initiation and elongation are modulated at non-synaptic sites.
引用
收藏
页码:1328 / 1337
页数:10
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