DAT
links: Dopamine reference: 10-24-2021
Dopamine Transporter (DAT) #
Unbound/excess dopamine is transported from the synaptic cleft into the presynaptic neuron via this.
- Low levels in ADHD in the left ventral Caudate, accumbal, midbrain, and hypothalamic regions. R
- MAO inhibition did not significantly affect densities in striatum, nucleus accumbens, medial forebrain bundle, or substantia nigra, nor did it affect DAT binding. R
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Phosphorylation #
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[Phosphorylation Mechanisms in Dopamine Transporter Regulation]
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‘PKC domain’: (Ser2/4/7/12/13/21. Less dopamine reuptake, more efflux
- CAMK II: Ser-13
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Thr53 (MAPK domain):more dopamine efflux (Amphetamine)
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Protein Kinase A phosphorylation (@ Ser7) causes it to internalize into the neuron and cease.
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Protein Kinase C phosphorylation does either that, or reverses DAT’s mechanism!
- Amphetamine causes this.
Genes #
- Encoded by SLC6A3.
- Variant T356M reverses the function of DAT, making it spew out dopamine. Dooesn’t respond to amphetamine treatment. Both of these functions can be restored by adding zinc to the cells.
- Variant A346V educes dopamine uptake, but is enriched in the membranes of cells (whatever that implies.)
- Variant R51W doesn’t leak the neurotransmitter in response to amphetamine.