Proteasome Modulates Positive and Negative Translational Regulators in Long-Term Synaptic Plasticity

• DOI: 10.1523/jneurosci.3291-13.2014
• Publication Date: 2014-02-26T17:23:41Z
• Authors: Chenghai Dong; Svitlana V. Bach; Kathryn A. Haynes; Ashok N. Hegde
• Keywords: EIF4E; Proteolysis; EIF4G; Eukaryotic initiation factor

Proteolysis by the ubiquitin-proteasome pathway appears to have a complex role in synaptic plasticity, but its various functions remain be elucidated. Using late phase long-term potentiation (L-LTP) hippocampus of mouse as model for we previously showed that inhibition proteasome enhances induction blocks maintenance L-LTP. In this study, investigated possible mechanisms which has opposite effects on L-LTP and maintenance. Our results show inhibiting phosphatidyl inositol-3 kinase or blocking interaction between eukaryotic initiation factors 4E (eIF4E) 4G (eIF4G) reduces enhancement brought about suggesting interplay proteolysis signaling mediated mammalian target rapamycin (mTOR). Also, leads accumulation translational activators mTOR such eIF4E elongation factor 1A (eEF1A) early during causing increased induction. Furthermore, causes buildup repressors, polyadenylate-binding protein interacting 2 (Paip2) 4E-binding (4E-BP2), stages contributing blockade Thus, plays critical regulating synthesis tightly controlling translation. provide novel mechanistic insights into degradation plasticity.