http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Laporte, Ste´phane A.,Miller, William E.,Kim, Kyeong-Man,Caron, Marc G. 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-
β-Arrestins, proteins involved in the turn-off of G protein-coupled receptor (GPCR) activation, bind to the β_2-adaptin subunit of the clathrin adaptor AP-2. The interaction of β_2-adaptin with β-Arrestin involves critical arginine residues in the C-terminal domain of β-Arrestin and plays an important role in initiating clathrin-mediated endocytosis of the β_2-adrenergic receptor(β_2AR) (Laporte, S. A., Oakley, R. H., Holt, J. A., Barak, L. S., and Caron, M. G. (2000) J. Biol. Chem. 276, 23120-23126). However, the β-arrestin-binding site in β_2-adaptin has not been identified, and little is known about the role of β-arrestin/AP-2 interaction in the endocytosis of other GPCRs. Using in vitro binding assays, we have identified two glutamate residues (Glu-849 and Glu-902) in β_2-adaptin that are important in β-arrestin binding. These residues are located in the platform subdomain of the C terminus β_2-adaptin, where accessory/adapter endocytic proteins for other classes of receptors interact, distinct from the main site where clathrin interact. The functional significance of the β-arrestin/AP-2/clathrin complex in the endocytosis of GPCRs such as the β_2AR and vasopressin type Ⅱ receptor was evaluated using mutant constructs of the β_2-adaptin C terminus containing either the clathrin and the β-arrestin binding domains or the β-arrestin-binding domain alone. When expressed in human embryonic kidney 293 cells, both constructs acted as dominant negatives inhibiting the agonist-induced internalization of the β_2AR and the vasopressin type Ⅱ receptor. In addition, although the β_2-adaptin construct containing both the clathrin and β-arrestin binding domains was able to block the endocytosis of transferrin receptors, a β_2-adaptin construct capable of assoociating with β-arrestin but lacking its high affinity clathrin interaction did not interfere with transferrin receptor endocytosis. These results suggest that the interaction of β-arrestin with β_2-adaptin represents a selective endocytic trigger for several members of the GPCR family.
Torres, Gonzalo E.,Yao, Wei-Dong,Mohn, Amy R.,Quan, Hui,Kim, Kyeong-Man,Levey, Allan I.,Staudinger, Jeff,Caron, Marc G. 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-
PDZ domain-containing proteins play an important role in the targeting and localization of synaptic membrane proteins. Here, we report an interaction between the PDZ domain-containing protein PICK1 and monoamine neurotransmitter transporters in vitro and in vivo. In dopaminergic neurons, PICK1 colocalizes with the dopamine transporter (DAT) and forms a stable protein complex. Coexpression of PICK1 with DAT in mammalian cells and neurons in culture results in colocalization of the two proteins in a cluster pattern and an enhancement of DAT uptake activity through an increase in the number of plasma membrane DAT. Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its association with PICK1 and impairs the localization of the transporter in neurons. These findings indicate a role for PDZ-mediated protein interactions in the localization, expression, and function of monoamine transporters.