GSE121162
The differences in local translatome across distinct neuron types is mediated by both baseline cellular differences and post-transcriptional mechanisms
Local translation in neurites is a phenomenon that enhances spatial segregation of proteins and their functions away from the cell body, yet it is unclear how local translation varies across neuronal cell types. Further, it is unclear if differences in local translation across cell types simply reflect differences in transcription or if there is also a cell type specific posttranscriptional regulation of the location and translation of specific mRNAs. Most of the mRNAs discovered as locally translated have been identified from hippocampal neurons because their laminar organization facilitates neurite specific dissection and microscopy methods. Given the diversity of neurons across the brain, studies have not yet analyzed how locally translated mRNAs differ across cell types, particularly those with neurites intertwined into other cell types. Here, we used the SynapTRAP method to harvest two broad cell types in the forebrain: GABAergic neurons and pyramidal neurons. While some transcripts overlap, the majority of the local translatome is not shared across these cell types. While most differences are driven by baseline expression levels in the respective cells, some transcripts also evidence cell type specific post transcriptional regulation of localization. Finally, we provide evidence that GABAergic neurons specifically localize mRNAs for peptide neurotransmitters, including somatostatin and cortistatin, suggesting localized production of these key signaling molecules in the neurites of GABAergic neurons. Overall, this work suggests that differences in local translation in neurites across neuronal cell types are poised to contribute substantially to the variability between cells. Overall design: 5 Replicates of 4 sample types, collect from two cell types each in the brain.