Ribosome association contributes to restricting mRNAs to the cell body of hippocampal neurons

In neurons, mRNAs are differentially sorted to axons, dendrites, and the ce ll body. Recently, regions of certain mRNAs have been identified that targe t those mRNAs for translocation to the processes. However, the mechanism by which many, if not most mRNAs are retained in the cell body is not underst ood. Total inhibition of translation, by puromycin or cycloheximide, result s in the mislocalization of cell body mRNAs to dendrites. We have examined the effect of translational inhibitors on the localization of ferritin mRNA , the translation of which can also be inhibited specifically by reducing i ron levels. Using nonisotopic in situ hybridization, ferritin mRNA is found restricted to the cell body of cultured rat hippocampal neurons. Following treatment with either puromycin or cycloheximide, it migrates into dendrit es. Control experiments reveal that the drugs affect neither the viability of the neuronal cultures, nor the steady-state level of ferritin mRNA. When transcription and protein synthesis are inhibited simultaneously, ferritin mRNA is found in the dendrites of puromycin, but not of cycloheximide-trea ted neurons. However, the localization of ferritin mRNA is unaffected by ch anges in iron concentration that regulate its translation rate specifically . We propose a model whereby cell body-restricted mRNAs are maintained in t hat location by association with ribosomes and with another cell component, which traps mRNAs when they are freed of ribosome association. The release of all mRNA species, as happens after total protein synthesis inhibition, floods the system and allows cell body mRNAs to diffuse into dendrites. In contrast, the partial release of the single ferritin mRNA species does not saturate the trapping system and the mRNA is retained in the cell body.