Received for publication January 7, 2008.
Revised April 24, 2008.
Accepted for publication April 28, 2008.

Novel Interaction of the Dopamine D₂ Receptor and the Ca²⁺-Binding Protein S100B: Role in D₂ Receptor Function

Abstract

S100B is a calcium binding protein with both extracellular and intracellular regulatory activities in the mammalian brain. We have identified a novel interaction between S100B and the dopamine D₂ receptor. Our results also suggest that the binding of S100B to the dopamine D₂ receptor enhances receptor signaling. This conclusion is based on the following observations: 1) S100B and the third cytoplasmic loop of the dopamine D₂ receptor interact in a bacterial two-hybrid system and in a polyHis pull-down assay; 2) immunoprecipitation of the D₂ receptor also precipitates FLAG-S100B from human embryonic kidney 293 cell homogenates and endogenous S100B from rat neostriatal homogenates; 3) S100B immunoreactivity was detected in cultured neostriatal neurons expressing the D₂ receptor; 4) a putative S100B binding motif is located at residues 233-240 of the D₂ receptor, towards the amino terminus of the third cytoplasmic loop. D₃-IC3, which does not bind S100B, does not contain this motif; 5) co-expression of S100B in D₂ receptor-expressing 293 cells selectively increased D₂ receptor stimulation of extracellular signal-regulated kinases and inhibition of adenylate cyclase.

Key words: Dopamine, Adenylyl cyclases, MAP Kinase

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