title: Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking.
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.-Lee, S.-A., Suh, Y., Lee, S., Jeong, J., Kim, S. J., Kim, S. J., Park, S. K. Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Seol-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Yeongjun
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Saebom
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea skpark@postech.ac.kr.
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D021381:Protein Transport; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; C404405:TSPAN7 protein, human; D059470:Tetraspanins
keywords: cell surface trafficking; dopaminergic signaling; endocytosis