Commentary on Novel interaction of the dopamine D2 receptor and the Ca2+ binding protein S100B: Role in D2 receptor function

Hun Joo Lee, Dayana Rodriguez-Contreras, Kim A. Neve

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

We previously proposed that the dopamine D2 receptor-interacting protein S100B binds to a putative S100B-binding motif at residues R233-L240 toward the N terminus of the third intracellular loop. We used in vitro pull-down assays with FLAG-tagged fragments of the rat dopamine D2 receptor third intracellular loop (D2-IC3) and in vitro-synthesized S100B to evaluate this hypothesis. Our results indicate that the putative S100B-binding motif is neither necessary nor sufficient for strong binding of S100B to D2-IC3. Instead, two residues at the junction of the fifth membrane-spanning domain and the cytoplasmic extension of that α-helical domain, K211-I212, are required for robust, calcium-sensitive binding of S100B. This is also the approximate location of previously identified determinants for the binding of arrestin and calmodulin. A D2 receptor mutation converting I212 to phenylalanine has been described in patients with a hyperkinetic movement disorder. SIGNIFICANCE STATEMENT S100B is a small calcium-binding protein that modulates signaling by the dopamine D2 receptor. New data suggest that the previous hypothesis about the involvement of an S100B-binding motif is incorrect, and that an important determinant of S100B binding includes a residue that is mutated in patients with a hyperkinetic movement disorder.

Original languageEnglish (US)
Pages (from-to)61-64
Number of pages4
JournalMolecular pharmacology
Volume100
Issue number2
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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