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Subcellular proteomics of dopamine neurons in the mouse brain reveals axonal enrichment of proteins encoded by Parkinson’s disease-linked genes

Benjamin D. Hobson, Se Joon Choi, Rajesh K. Soni, David Sulzer, Peter A. Sims
doi: https://doi.org/10.1101/2021.06.01.446584
Benjamin D. Hobson
1Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032
2Medical Scientist Training Program, Columbia University Irving Medical Center, New York, NY 10032
4Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032
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Se Joon Choi
6Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032
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Rajesh K. Soni
7Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032
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David Sulzer
3Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032
4Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032
5Department of Pharmacology, Columbia University Irving Medical Center, New York, NY 10032
6Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032
10Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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  • For correspondence: pas2182@cumc.columbia.edu ds43@cumc.columbia.edu
Peter A. Sims
1Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032
8Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032
9Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY 10032
10Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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  • For correspondence: pas2182@cumc.columbia.edu ds43@cumc.columbia.edu
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Abstract

Dopaminergic neurons modulate neural circuits and behaviors via dopamine 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 a significant enrichment of proteins encoded by Parkinson’s disease-linked genes in striatal dopaminergic axons, including proteins 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://www.ebi.ac.uk/pride/archive/projects/PXD026229

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 01, 2021.
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Subcellular proteomics of dopamine neurons in the mouse brain reveals axonal enrichment of proteins encoded by Parkinson’s disease-linked genes
Benjamin D. Hobson, Se Joon Choi, Rajesh K. Soni, David Sulzer, Peter A. Sims
bioRxiv 2021.06.01.446584; doi: https://doi.org/10.1101/2021.06.01.446584
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Subcellular proteomics of dopamine neurons in the mouse brain reveals axonal enrichment of proteins encoded by Parkinson’s disease-linked genes
Benjamin D. Hobson, Se Joon Choi, Rajesh K. Soni, David Sulzer, Peter A. Sims
bioRxiv 2021.06.01.446584; doi: https://doi.org/10.1101/2021.06.01.446584

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