Membrane trafficking regulates the activity of the human dopamine transporter.

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Melikian HE, Buckley KM

Membrane trafficking regulates the activity of the human dopamine transporter.

J Neurosci. 1999 Sep 15;19(18):7699-710.

PubMed ID

10479674 [ View in PubMed

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Abstract

The trafficking of synaptic proteins is unquestionably a major determinant of the properties of synaptic transmission. Here, we present a detailed analysis of the downregulation and intracellular trafficking of the cocaine- and amphetamine-sensitive dopamine transporter (DAT), a presynaptic plasma membrane protein responsible for the regulation of extracellular DA concentrations. Using PC12 cells stably transfected with human DAT cDNA, we observe that phorbol ester activation of protein kinase C (PKC) results in decreased transporter capacity and a parallel decrease in the amount of DAT on the cell surface that is attributable to intracellular transporter sequestration. After internalization, DAT diverges to the recycling, as opposed to the degradative, arm of the endocytic pathway. This study demonstrates, for the first time, DAT endocytosis, establishes the pathways through which DAT traffics both at steady state and in response to PKC activation, and suggests that DAT recycling is likely to occur.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Imipramine	Sodium-dependent dopamine transporter	Protein	Humans	Unknown	Inhibitor	Details