Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation

Madhur Shetty, Danielle E. Bolland, Joshua Morrell, Bryon D. Grove, James D. Foster, Roxanne A. Vaughan

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

The primary regulator of dopamine availability in the brain is the dopamine transporter (DAT), a plasma membrane protein that drives reuptake of released dopamine from the extracellular space into the presynaptic neuron. DAT activity is regulated by post-translational modifications that establish clearance capacity through impacts on transport kinetics, and dysregulation of these events may underlie dopaminergic imbalances in mood and psychiatric disorders. Here, using fluorescence recovery after photobleaching, we show that phosphorylation and palmitoylation induce opposing effects on DAT lateral membrane mobility, which may influence functional outcomes by regulating subcellular localization and binding partner interactions. Membrane mobility was also impacted by amphetamine and in polymorphic variant A559V in directions consistent with enhanced phosphorylation. These findings grow the list of DAT properties controlled by these post-translational modifications and highlight their role in establishment of dopaminergic tone in physiological and pathophysiological states.

Original languageEnglish (US)
Article number100106
JournalCurrent Research in Physiology
Volume6
DOIs
StatePublished - Jan 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • 2-Bromopalmitate
  • Amphetamine
  • DHHC2
  • FRAP
  • Fluorescence recovery after photobleaching
  • Mitogen activated protein kinase
  • Palmitoyl acyl transferase
  • Protein kinase C

PubMed: MeSH publication types

  • Journal Article
  • Review

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