Axonal and somatodendritic proteomes of dopamine neurons in the mouse brain
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ABSTRACT: Dopamine (DA) neurons modulate neural circuits and behaviors via dopamine release from expansive, long range axonal projections. The elaborate cytoarchitecture of DA neurons is embedded within complex brain tissues, making it difficult to access the DA 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 DA neurons. Our dataset reveals the proteomic architecture underlying axonal transport, dopamine transmission, and axonal metabolism in DA neurons. We find a significant enrichment of proteins encoded by Parkinson’s disease-linked genes in dopaminergic axons, including proteins with previously undescribed axonal localization. Our proteomic datasets comprise a significant resource for axonal and DA neuronal cell biology, while the methodology developed here will enable future studies of other neural cell types.
INSTRUMENT(S): Orbitrap Fusion
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain, Dopaminergic Neuron
DISEASE(S): Disease Free
SUBMITTER: Peter Sims
LAB HEAD: Peter Sims
PROVIDER: PXD026229 | Pride | 2021-06-01
REPOSITORIES: Pride
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