Cdc42 plays a requisite role in dopamine transporter endocytic trafficking (896.6)

Ack1 is a dopamine transporter endocytic brake that rescues a trafficking-dysregulated ADHD coding variant.

The dopamine (DA) transporter (DAT) facilitates high-affinity presynaptic DA reuptake that temporally and spatially constrains DA neurotransmission. Aberrant DAT function is implicated in attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is a major psychostimulant target, and psychostimulant reward strictly requires binding to DAT. DAT function is acutely modulated by d...

Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton.

Dopaminergic signaling profoundly impacts rewarding behaviors, movement, and executive function. The presynaptic dopamine (DA) transporter (DAT) recaptures released DA, thereby limiting synaptic DA availability and maintaining dopaminergic tone. DAT constitutively internalizes and PKC activation rapidly accelerates DAT endocytosis, resulting in DAT surface loss. Longstanding evidence supports P...

Epitope-tagged dopamine transporter knock-in mice reveal rapid endocytic trafficking and filopodia targeting of the transporter in dopaminergic axons.

The plasma membrane dopamine (DA) transporter (DAT) is essential for reuptake of extracellular DA. DAT function in heterologous cells is regulated by subcellular targeting, endocytosis, and intracellular trafficking, but the mechanisms regulating neuronal DAT remain poorly understood. Hence, we generated a knock-in mouse expressing a hemagglutinin (HA)-epitope-tagged DAT to study endogenous tra...

Role of Sortilin in the Post-endocytic Trafficking of Thyroglobulin

Membrane trafficking regulates the activity of the human dopamine transporter.

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 cel...