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Localization of a Β-Actin Messenger Ribonucleoprotein Complex with Zipcode-Binding Protein Modulates the Density of Dendritic Filopodia and Filopodial Synapses

Department of Neuroscience, Rose F. Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 12/2003; 23(32):10433-44.
Source: PubMed

ABSTRACT The dendritic transport and local translation of mRNA may be an essential mechanism to regulate synaptic growth and plasticity. We investigated the molecular mechanism and function of beta-actin mRNA localization in dendrites of cultured hippocampal neurons. Previous studies have shown that beta-actin mRNA localization to the leading edge of fibroblasts or the growth cones of developing neurites involved a specific interaction between a zipcode sequence in the 3' untranslated region and the mRNA-binding protein zipcode-binding protein-1 (ZBP1). Here, we show that ZBP1 is required for the localization of beta-actin mRNA to dendrites. Knock-down of ZBP1 using morpholino antisense oligonucleotides reduced dendritic levels of ZBP1 and beta-actin mRNA and impaired growth of dendritic filopodia in response to BDNF treatment. Transfection of an enhanced green fluorescent protein (EGFP)-beta-actin construct, which contained the zipcode, increased the density of dendritic filopodia and filopodial synapses. Transfection of an EGFP construct, also with the zipcode, resulted in recruitment of endogenous ZBP1 and beta-actin mRNA into dendrites and similarly increased the density of dendritic filopodia. However, the beta-actin zipcode did not affect filopodial length or the density of mature spines. These results reveal a novel function for an mRNA localization element and its binding protein in the regulation of dendritic morphology and synaptic growth via dendritic filopodia.

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    • "For example, localization of the beta-actin protein requires a 54- nucleotide cis-acting zip code in the 3 UTR to target it to dendrites and growth cones (Kislauskis and Singer, 1992; Zhang et al., 1999; Eom et al., 2003). "
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    • "Distinct microRNAs are localized to specific subcellular compartments (Han et al., 2011; Kaplan et al., 2013; Sasaki et al., 2014), suggesting that they regulate the composition of locally translatable mRNAs by degrading or silencing their target mRNAs. Localization elements exhibit modularity, as they are functional even when ectopically fused to a reporter mRNA (Eom et al., 2003). Many mRNAs contain multiple cis-elements exhibiting both redundancy and diversity. "
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    • "Cocaine also induces long-lasting alterations in dendritic length, spine density, and the number of branched spines in the striatum (Robinson and Kolb 1999). Localized translation of mRNA in this compartment is thought to be involved in these structural alterations (Eom et al. 2003); therefore, our data raise the possibility that regulating local translation of mRNAs in the Nucleus Accumbens may play a role in cocaine cue reactivity in vivo. "
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