TY - JOUR
T1 - The differences in local translatome across distinct neuron types is mediated by both baseline cellular differences and posttranscriptional mechanisms
AU - Ouwenga, Rebecca
AU - Lake, Allison M.
AU - Aryal, Shivani
AU - Lagunas, Tomas
AU - Dougherty, Joseph D.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH; Grants R21-MH-099798, R01-NS-102272, 5U01-MH-109133, R33 DA041883, and R01-NS-078398). Key technical support was provided by the Genome Technology Resource Center at Washington University (supported by NIH Grants P30-CA-91842, UL1-TR-000448, and UL1-TR-002345), and the Hope Center Viral Vectors core at Washington University School of Medicine. R.O. was supported by National Research Service Award Grant T32-GM-081739. J.D.D. is a NARSAD investigator.
Publisher Copyright:
© 2018 Ouwenga et al.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - GABAergic interneurons
KW - Layer 5 pyramidal neurons
KW - Local translation
KW - Synap- TRAP
KW - Synaptoneurosomes
KW - TRAP
UR - http://www.scopus.com/inward/record.url?scp=85061160375&partnerID=8YFLogxK
U2 - 10.1523/ENEURO.0320-18.2018
DO - 10.1523/ENEURO.0320-18.2018
M3 - Article
C2 - 30723792
AN - SCOPUS:85061160375
SN - 2373-2822
VL - 5
JO - eNeuro
JF - eNeuro
IS - 6
M1 - e0320-18.2018
ER -