TY - JOUR
T1 - Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders
T2 - Proteins interacting with the third cytoplasmic loop of dopamine D2 and D3 receptors
AU - Shioda, Norifumi
AU - Takeuchi, Yusuke
AU - Fukunaga, Kohji
PY - 2010
Y1 - 2010
N2 - Among the various dopamine receptors, D2-like receptors (D2R, D3R, and D4R) are characterized by a large third cytoplasmic loop, a short carboxyl-terminal tail, and the ability to activate inhibitory G proteins. The diverse activities of D2-like receptors are partly mediated by proteins that interact with the third cytoplasmic loop, which regulate receptor signaling, receptor trafficking, and stability. Furthermore, in the case of D2R and D3R genes, mRNA splicing generates isoforms in the region of the third cytoplasmic loop. The gene encoding D2R gives rise to two isoforms, termed the dopamine D2 receptor long isoform (D2LR) and the dopamine D2 receptor short isoform (D2SR), which lacks 29 amino acids of the D2LR within the third cytoplasmic loop. The D3R gene also produces at least seven distinct alternative splicing variants including D3nf, in which 98 base pairs in the carboxyl-terminal region of the third intracellular loop are deleted. In this review, we focus on proteins interacting with the dopamine D2/D3 receptors in the third cytoplasmic loop. We also define a novel binding protein, heart-type fatty acid-binding protein (HFABP), which specifically interacts with the 29 D2LR amino acids deleted in D2SR and document its function in D2LR signaling.
AB - Among the various dopamine receptors, D2-like receptors (D2R, D3R, and D4R) are characterized by a large third cytoplasmic loop, a short carboxyl-terminal tail, and the ability to activate inhibitory G proteins. The diverse activities of D2-like receptors are partly mediated by proteins that interact with the third cytoplasmic loop, which regulate receptor signaling, receptor trafficking, and stability. Furthermore, in the case of D2R and D3R genes, mRNA splicing generates isoforms in the region of the third cytoplasmic loop. The gene encoding D2R gives rise to two isoforms, termed the dopamine D2 receptor long isoform (D2LR) and the dopamine D2 receptor short isoform (D2SR), which lacks 29 amino acids of the D2LR within the third cytoplasmic loop. The D3R gene also produces at least seven distinct alternative splicing variants including D3nf, in which 98 base pairs in the carboxyl-terminal region of the third intracellular loop are deleted. In this review, we focus on proteins interacting with the dopamine D2/D3 receptors in the third cytoplasmic loop. We also define a novel binding protein, heart-type fatty acid-binding protein (HFABP), which specifically interacts with the 29 D2LR amino acids deleted in D2SR and document its function in D2LR signaling.
KW - Alternative splicing variant
KW - Catalepsy
KW - Heart-type fatty acid-binding protein
UR - http://www.scopus.com/inward/record.url?scp=77957935835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957935835&partnerID=8YFLogxK
U2 - 10.1254/jphs.10R02FM
DO - 10.1254/jphs.10R02FM
M3 - Review article
C2 - 20716856
AN - SCOPUS:77957935835
VL - 114
SP - 25
EP - 31
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 1
ER -