yana-notes

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

Phosphorylation #

  • [Phosphorylation Mechanisms in Dopamine Transporter Regulation]

  • ‘PKC domain’: (Ser2/4/7/12/13/21. Less dopamine reuptake, more efflux

  • Thr53 (MAPK domain):more dopamine efflux (Amphetamine)

  • Protein Kinase A phosphorylation (@ Ser7) causes it to internalize into the neuron and cease.

  • Protein Kinase C phosphorylation does either that, or reverses DAT’s mechanism!

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.