Subcellular and regional localization of mRNA translation in midbrain dopamine neurons

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. [Display omitted] •No evidence of mRNA translation in dopaminergic axons in the mouse brain•Dopaminergic dendrites contain ribosomes and mRNA encoding DA transmission proteins•Dendritic localization of mRNAs and exocytic fusion proteins•Molecular signature of SNr mDA neurons, including Atp2a3/SERCA3, an ER calcium pump Local translation regulates the subcellular proteome in neurons but has not been characterized in midbrain dopamine neurons, cells with large dendrites and axonal arborizations. Hobson et al. investigate messenger RNA localization and translation in midbrain dopamine neurons in the mouse brain, finding ribosomes and dopaminergic mRNAs in dendrites, but not axons.