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Publication : CPEB2 Activates GRASP1 mRNA Translation and Promotes AMPA Receptor Surface Expression, Long-Term Potentiation, and Memory.

First Author  Lu WH Year  2017
Journal  Cell Rep Volume  21
Issue  7 Pages  1783-1794
PubMed ID  29141213 Mgi Jnum  J:254876
Mgi Id  MGI:6104123 Doi  10.1016/j.celrep.2017.10.073
Citation  Lu WH, et al. (2017) CPEB2 Activates GRASP1 mRNA Translation and Promotes AMPA Receptor Surface Expression, Long-Term Potentiation, and Memory. Cell Rep 21(7):1783-1794
abstractText  Activity-dependent synthesis of plasticity-related proteins is necessary to sustain long-lasting synaptic modifications and consolidate memory. We investigated the role of the translational regulator cytoplasmic polyadenylation element binding protein 2 (CPEB2) in learning and memory because regulated mRNA translation contributes to synaptic plasticity. Forebrain-restricted CPEB2 conditional knockout (cKO) mice exhibited impaired hippocampus-dependent memory in contextual fear conditioning and Morris water maze tests. CPEB2 cKO hippocampi showed impaired long-term potentiation in the Schaffer collateral-CA1 pathway. Reduced surface, but not total, expression of AMPA receptors (AMPARs) in CPEB2 KO neurons led us to identify that CPEB2 enhanced the translation of GRASP1 mRNA to facilitate recycling and maintain the surface level of AMPARs. Ectopic expression of CPEB2 or GRASP1 in CA1 areas of CPEB2 cKO mouse hippocampi rescued long-term potentiation and spatial memory in a water maze test. Thus, CPEB2-regulated GRASP1 mRNA translation is pivotal for AMPAR recycling, long-term plasticity, and memory.
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