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July 1, 2026Communications BiologyOpen Access

Gαo/z-biased coupling profile of the dopamine D3 receptor

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Authors

LZLucrezia ZanettiLFLuca FranchiniSSShirsha Saha

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Overview

Randomized trial characterizes G protein coupling and signaling in dopamine D3 receptors, indicating distinct therapeutic potentials.

Key Points

  • This research aims to analyze the G protein coupling of dopamine D3 receptors to inform safer drug design for neuropsychiatric disorders.
  • Characterized G protein coupling using cell-based assays with wild-type and ΔGαi/o/z cells.
  • Analyzed D3R and D2R chimeras to identify molecular determinants of Gαi coupling inhibition.
  • Utilized cryo-EM structures to model the receptor interface for insight into selectivity.
  • D3R exclusively activates Gαo/z subtypes and does not engage with Gαi proteins.
  • Structural determinants for selectivity were identified in the α5 helix of Gαi and ICL2 of D3R.
  • Hippocampal neuron assays show distinct regulation of adenylyl cyclase and cAMP by D3R agonists and antagonists.

Cite This Study

Zanetti et al. (2026) studied this question.

synapsesocial.com/papers/6a44ad765cd2549c8bc430d5https://doi.org/10.1038/s42003-026-10587-0
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