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Journal of Neuroscience, Vol 16, 436-447, Copyright © 1996 by Society for Neuroscience
The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons
MJ Nirenberg, RA Vaughan, GR Uhl, MJ Kuhar and VM Pickel
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
Nigrostriatal dopaminergic neurons play an essential role in the central
regulation of motor functions. These functions are initiated through the
release of dopamine from axon terminals in the striatum or from dendrites
in the substantia nigra (SN) and are terminated by the reuptake of dopamine
by the sodium- and chloride-dependent dopamine transporter (DAT). DAT also
can transport dopamine neurotoxins and has been implicated in the selective
vulnerability of nigrostriatal dopaminergic neurons in major models of
Parkinson's disease. We have used electron microscopic immunocytochemistry
with an N-terminal domain anti-peptide antibody to examine the subcellular
distribution of DAT in the rat SN and dorsolateral striatum. In the SN,
immunogold labeling for DAT was localized to cytoplasmic surfaces of plasma
membranes and smooth endoplasmic reticulum of dendrites and dendritic
spines, few of which contained synaptic vesicles. Neuronal perikarya in the
SN contained immunogold-labeled pleomorphic electron-lucent tubulovesicles
but showed immunolabeling of plasma membranes only rarely. Axon terminals
in the striatum contained extensive immunogold labeling of cytoplasmic
surfaces of plasma membranes near aggregates of synaptic vesicles and less
frequent labeling of intervaricose segments of plasma membrane or small
electron-lucent vesicles. In sections dually labeled for DAT and the
catecholamine-synthesizing enzyme tyrosine hydroxylase, both markers were
colocalized in most profiles in the SN and striatum. These findings support
the proposed topological model for DAT and suggest that this transporter is
strategically located to facilitate uptake of dopamine and neurotoxins into
distal dendritic and axonal processes of nigrostriatal dopaminergic
neurons.
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[Abstract]
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