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Publication : Subcellular proteomics of dopamine neurons in the mouse brain.

First Author  Hobson BD Year  2022
Journal  Elife Volume  11
PubMed ID  35098924 Mgi Jnum  J:322648
Mgi Id  MGI:6885196 Doi  10.7554/eLife.70921
Citation  Hobson BD, et al. (2022) Subcellular proteomics of dopamine neurons in the mouse brain. Elife 11:e70921
abstractText  Dopaminergic neurons modulate neural circuits and behaviors via dopamine (DA) release from expansive, long range axonal projections. The elaborate cytoarchitecture of these neurons is embedded within complex brain tissue, making it difficult to access the neuronal proteome using conventional methods. Here, we demonstrate APEX2 proximity labeling within genetically targeted neurons in the mouse brain, enabling subcellular proteomics with cell-type specificity. By combining APEX2 biotinylation with mass spectrometry, we mapped the somatodendritic and axonal proteomes of midbrain dopaminergic neurons. Our dataset reveals the proteomic architecture underlying proteostasis, axonal metabolism, and neurotransmission in these neurons. We find that most proteins encoded by DA neuron-enriched genes are localized within striatal dopaminergic axons, including ion channels with previously undescribed axonal localization. These proteomic datasets provide a resource for neuronal cell biology, and this approach can be readily adapted for study of other neural cell types.
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