| Autor: |
Ouwenga R; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110., Lake AM; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110., Aryal S; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri 63110., Lagunas T Jr; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110., Dougherty JD; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110. |
| Abstrakt: |
Local translation in neurites is a phenomenon that enhances the 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 whether differences in local translation across cell types simply reflect differences in transcription or whether there is also a cell type-specific post-transcriptional regulation of the location and translation of specific mRNAs. Most of the mRNAs discovered as being 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. Here, we used the SynapTRAP method to harvest two broad cell types in the mouse forebrain: GABAergic neurons and layer 5 projection neurons. While some transcripts overlap, the majority of the local translatome is not shared across these cell types. In addition to differences driven by baseline expression levels, some transcripts also exhibit cell type-specific post-transcriptional regulation. 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 heterogeneity in neuronal phenotypes. |
