Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280).
Proteins that bind to G protein-coupled receptors have been identified as regulators of receptor localization and signaling. In our previous studies, a cytoskeletal protein, actin-binding protein 280 (ABP-280), was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D(3) receptors, but not with D(4) receptors. Similar to the dopamine D(2) receptor, the D(3)/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280, D(3) receptors were unable to inhibit forskolin-stimulated cyclic AMP (cAMP) production significantly. D(4) receptors, however, exhibited a similar degree of inhibition of forskolin-stimulated cAMP production in ABP-280-deficient M2 cells and ABP-280-replent M2 subclones (A7 cells). Further experiments revealed that the D(3)/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D(3) receptor third loop, which is conserved in the D(2) receptor but not in the D(4) receptor. Our results demonstrate a subtype-specific regulation of dopamine D(2)-family receptor signaling by the cytoskeletal protein ABP-280.
Li
Ming
M
Department of Pharmacology, University of California, Room 360, Med. Surge II, Irvine, CA 92697-4625, USA.
Li
Chuanyu
C
Weingarten
Paul
P
Bunzow
James R
JR
Grandy
David K
DK
Zhou
Qun Yong
QY
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D000067956:Adenylyl Cyclase Inhibitors; D003285:Contractile Proteins; C493593:DRD3 protein, human; C578661:FLNC protein, human; D064448:Filamins; D008840:Microfilament Proteins; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000262:Adenylyl Cyclases