Subcellular and regional localization of mRNA translation in midbrain dopamine neurons

Benjamin D. Hobson, Linghao Kong, Maria Florencia Angelo, Ori J. Lieberman, Eugene V. Mosharov, Etienne Herzog, David Sulzer, Peter A. Sims
Cell Reports. 2022-01-01; 38(2): 110208
DOI: 10.1016/j.celrep.2021.110208

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Hobson BD(1), Kong L(2), Angelo MF(3), Lieberman OJ(4), Mosharov EV(5), Herzog E(6), Sulzer D(7), Sims PA(8).

Author information:
(1)Department of Systems Biology, Columbia University Irving Medical Center, New York 10032, NY, USA; Medical Scientist Training Program, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.
(2)Department of Systems Biology, Columbia University Irving Medical Center, New
York 10032, NY, USA.
(3)Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
(4)Medical Scientist Training Program, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.
(5)Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
(6)Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France. Electronic address: .
(7)Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Pharmacology, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Molecular
Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USA. Electronic address: .
(8)Department of Systems Biology, Columbia University Irving Medical Center, New York 10032, NY, USA; Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA; Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USA. Electronic address: .

Midbrain dopaminergic (mDA) neurons exhibit extensive dendritic and axonal arborizations, but local protein synthesis is not characterized in these neurons. Here, we investigate messenger RNA (mRNA) localization and translation in mDA neuronal axons and dendrites, both of which release dopamine (DA). Using highly sensitive ribosome-bound RNA sequencing and imaging approaches, we find no evidence for mRNA translation in mDA axons. In contrast, mDA neuronal dendrites in the substantia nigra pars reticulata (SNr) contain ribosomes and mRNAs encoding the major components of DA synthesis, release, and reuptake machinery. Surprisingly, we also observe dendritic localization of mRNAs encoding synaptic vesicle-related proteins, including those involved in exocytic fusion. Our results are consistent with a role for local translation in the regulation of DA release from dendrites, but not from axons. Our translatome data define a molecular signature of sparse mDA neurons in the SNr, including the enrichment of Atp2a3/SERCA3, an atypical ER calcium pump.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs Bordeaux Neurocampus