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- W792569085 abstract "Fig. 1 CPEB function in neurons. Following NMDA receptor activation, the kinase (Aurora or CaMKII [Atkins et al., 2004]) is activated and phosphorylates CPEB. Phosphorylation stabil izes Cleavage and Polyadenylation Specificity Fac tor (CPSF ) on the AAUAAA hexanucleotide, which attracts poly(A) p o l y m e r a s e ( PA P ) t o c a t a l y z e polyadenylation. Maskin dissociates from eIF4E (cap binding protein). eIF4G then binds eIF4E and initiates translation. Long term potentiation (LTP) is a long lasting form of synaptic plasticity, thought to be the molecular correlate of learning and memory storage mechanisms [Kandel, 2001]. The enduring nature of LTP has been shown to involve Cytoplasmic Polyadenylation Element Binding proteins (CPEBs), a class of RNA-binding proteins modulating transcription-independent protein synthesis by regulating the poly(A)-tail elongation (Fig.1) [Richter, 2007]. Adapted from from Klann & Dever, 2004 CPEBs bind a conserved nucleotide sequence UUUUUAU (CPE) in the 3’UTR of the target mRNAs, and repress translation, unless phosphorylated. Such protein-mRNA complexes have beed found in dendritic spines of hippocampal neurons, and are likely targets for neuronal activity-induced translation. The 3’UTR mRNA of many key players in synaptic plasticity contain CPE elements. These includes tissue plasminogen activator (tPA) [Shin et al., 2004] – an extracellular protease implicated in neurodegeneration following seizures in mouse brain [Tsirka et al., 1995]. It has been shown that specifically tPA from microglial origin is the neurodegenerating factor [Siao et al., 2003]. CPEBs are present microglial (MG) cells and may regulate production of microglial tPA. In this study we investigate the expression pattern and function of microglial CPEBs and their potential link to tPA expression and temporal lobe epilepsy (TLE). Fig. 2 Tertiary structure of CPEBs. All four CPEBs expressed in mouse brain are structuralily similar, consistion of N-terminal regulatory domain (containing phosphorylation sites) and C-terminal RNA binding domain containing zink finger motif." @default.
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- W792569085 date "2009-01-01" @default.
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- W792569085 title "Elucidating the function of CPEB proteins in microglia" @default.
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