Commentary on "Novel Interaction of the Dopamine D2 Receptor and the Ca 2+ Binding Protein S100B: Role in D2 Receptor Function".

Autor:	Lee HJ; Research Service, VA Portland Health Care System, Portland, Oregon, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon., Rodriguez-Contreras D; Research Service, VA Portland Health Care System, Portland, Oregon, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon., Neve KA; Research Service, VA Portland Health Care System, Portland, Oregon, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon nevek@ohsu.edu.
Jazyk:	angličtina
Zdroj:	Molecular pharmacology [Mol Pharmacol] 2021 Aug; Vol. 100 (2), pp. 61-64. Date of Electronic Publication: 2021 May 27.
DOI:	10.1124/molpharm.121.000284
Abstrakt:	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. (U.S. Government work not protected by U.S. copyright.)
Databáze:	MEDLINE
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