845. Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons

Armaz Aschrafi,Anthony E Gioio,Lijin Dong,Barry Kaplan

doi:10.1016/j.biopsych.2017.02.570

Armaz Aschrafi, Anthony E Gioio + Show 2 more

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https://doi.org/10.1016/j.biopsych.2017.02.570

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Abstract

845. Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons

Highlights

It is evident that one of the mechanisms used by axons and presynaptic nerve terminals to rapidly respond to extracellular cues is to temporally and spatially regulate protein expression by asymmetrical mRNA transport and localized translation (Gomes et al, 2014; Jung et al, 2014)
We employed chimeric fluorescent reporter constructs and identified a sequence element within the Tyrosine hydroxylase (TH) 3’UTR that is required for the axonal localization of the reporter mRNA (Gervasi et al, 2016). These results provided the first direct evidence that TH mRNA is trafficked to the axon under the direction of a cis-acting regulatory element situated in the 3’UTR of the mRNA
It was hypothesized that the local translation of TH is critical for axonal TH activity and the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal

Summary

Introduction

It is evident that one of the mechanisms used by axons and presynaptic nerve terminals to rapidly respond to extracellular cues is to temporally and spatially regulate protein expression by asymmetrical mRNA transport and localized translation (Gomes et al, 2014; Jung et al, 2014). Transport of mRNAs into the distal axons enables coordination of local changes in the presynaptic proteome, a process critical in directing the growth cones of immature axons and ensuring neuronal survival (Fallini et al, 2016). The targeting of specific mRNAs to the distal structural/functional domains of the neuron is driven by sequence motifs located in the 3=untranslated region (3’UTR) of the RNA itself, which are recognized by specialized RNA-binding proteins (RBPs; Smart et al, 2007) These cis-acting regulatory elements or “zipcodes” contain localization signals (Aschrafi et al, 2010). The motifs can be constituted by either the primary sequence of the mRNA, or its higher order structure, such as a hairpin or stem-loop (Aschrafi et al, 2010; Di Liegro et al, 2014)

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