QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Related Article All Versions of this Article: mol.108.049098v1 74/2/317    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Related articles in MolPharm Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Stanwood, G. D. PubMed PubMed Citation Articles by Stanwood, G. D.

Perspective

Protein-Protein Interactions and Dopamine D₂ Receptor Signaling: A Calcium Connection

Department of Pharmacology, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee

The third cytoplasmic loop is a crucial site of physical contact between some G protein-coupled receptors (GPCRs) and their respective G proteins. However, interactions not only occur among these proteins but also involve a number of additional protein binding partners. Modulation of these protein-protein interactions may represent an important new avenue of pharmacotherapy through which signaling of GPCRs can be modulated. In the current issue of Molecular Pharmacology, Liu et al. (p. 371) report that dopamine D₂ receptors interact with the Ca²⁺ binding protein S100B. Using the third intracellular loop of the dopamine D₂ receptor as bait in a bacterial two-hybrid system, S100B was determined to be a potential binding partner. They used pull-down assays both in vitro and in vivo to confirm the interaction and define its specificity. Neither the D₃ nor the D₄ receptor expresses the motif conferring the interaction, and peptides based on the third intracellular loop of the D₃ receptor did not pull down S100B. Some groups might stop there, but Liu and colleagues moved on to demonstrate colocalization of the D₂ receptor and S100B by immunostaining. Functional assays were then used to show that coexpression of S100B with the D₂ receptor increases the ability of D₂ receptors to activate ERK and to inhibit adenylyl cyclase. These data suggest that S100B coexpression may serve as an important mediator of D₂ receptor signaling efficacy in the brain. These interactions contribute to cellular, regional, and developmental differences in D₂ receptor activation.

Address correspondence to: Dr. Gregg D. Stanwood, Department of Pharmacology, Vanderbilt Kennedy Center, 23rd Ave South, 476 RRB, Nashville TN 37232-6600. E-mail: gregg.stanwood{at}vanderbilt.edu

Related articles in MolPharm:

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

Yong Liu, David C. Buck, and Kim A. Neve
MolPharm 2008 74: 371-378. [Abstract] [Full Text]