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Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking SCIE SCOPUS

Title
Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking
Authors
Lee, S.-A.Suh, Y.Lee, S.Jeong, J.Kim, S.J.Kim, S.J.Park, S.K.
Date Issued
2017-06
Publisher
FASEB
Abstract
The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization. Immunocytochemical analysis revealed that TSPAN7 that resides in the plasma membrane and early and late endosomes promoted internalization of DRD2 and its localization to endosomal compartments of the endocytic pathway. Furthermore, we observed that TSPAN7 deficiency increased surface localization of DRD2 concurrent with the decrease of its endocytosis, regardless of dopamine treatment. Finally, TSPAN7 negatively affects DRD2-mediated signaling. These results disclosed a previously uncharacterized role of TSPAN7 in the regulation of the expression and functional activity of DRD2 by postendocytic trafficking. ? FASEB.
Keywords
dopamine 2 receptor; mitogen activated protein kinase 1; tetraspanin; tetraspanin 7; unclassified drug; dopamine 2 receptor; DRD2 protein, human; isoprotein; nerve protein; tetraspanin; TSPAN7 protein, human; Article; cell migration; cellular distribution; controlled study; endosome; HEK293 cell line; human; human cell; immunocytochemistry; priority journal; protein expression; protein function; protein localization; quantitative analysis; real time polymerase chain reaction; regulatory mechanism; steady state; surface property; animal; cell line; gene expression regulation; genetics; metabolism; physiology; protein transport; signal transduction; Animals; Cell Line; Gene Expression Regulation; Humans; Nerve Tissue Proteins; Protein Isoforms; Protein Transport; Receptors, Dopamine D2; Signal Transduction; Tetraspanins
URI
https://oasis.postech.ac.kr/handle/2014.oak/50890
DOI
10.1096/fj.201600755RR
ISSN
0892-6638
Article Type
Article
Citation
FASEB Journal, vol. 31, no. 6, page. 2301 - 2313, 2017-06
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박상기PARK, SANG KI
Dept of Life Sciences
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