Subcellular Vasopressin mRNA Trafficking and Local Translation in Dendrites


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Abstract

Vasopressin mRNA is delivered to axons and dendrites of rat hypothalamic magnocellular neurones. Subcellular localization of mRNAs requires sequences (cis-acting elements) within the RNA and proteins (trans-acting factors), which together mediate nucleic acid transport along the cytoskeleton to specific cytoplasmic destinations. In cultured neurones, vasopressin mRNA transcribed from a microinjected eukaryotic expression vector is sorted to dendrites. Detailed analyses revealed the presence of a complex cis-acting element, called dendritic localizer sequence (DLS), within part of the coding- and the 3′-untranslated region of vasopressin mRNA. Biochemical investigations have shown a specific interaction of poly(A)-binding protein (PABP) with the DLS. PABP is implicated in translation, translational control, RNA stability and RNA transport. Hence, PABP could be a component of a probably multifactor complex regulating transport and local translation of vasopressin mRNA. Dendrites are capable of translation. Local synthesis of the vasopressin precursor in dendrites of in vitro cultured neurones was demonstrated by microinjecting a vector encoding a mutant vasopressin polyprotein that is unable to leave the rough endoplasmic reticulum. Expression of this construct revealed that the nondiffusable protein is only detectable in dendrites harbouring vasopressin mRNA whereas dendrites devoid of this transcript lack the mutant vasopressin precursor.

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