Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein)
GABAA receptors are heteropentameric ligand-gated chloride channels composed of a variety of subunits, including α1 – 6, β1 – 3, γ1 – 3, δ, ε, θ, and π, and play a key role in controlling inhibitory neuronal activity. Modification of the efficacy of the synaptic strength is produced by changes in bo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319342252 |
| _version_ | 1818156788219904000 |
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| author | Takashi Kanematsu Akiko Mizokami Keiko Watanabe Masato Hirata |
| author_facet | Takashi Kanematsu Akiko Mizokami Keiko Watanabe Masato Hirata |
| author_sort | Takashi Kanematsu |
| collection | DOAJ |
| description | GABAA receptors are heteropentameric ligand-gated chloride channels composed of a variety of subunits, including α1 – 6, β1 – 3, γ1 – 3, δ, ε, θ, and π, and play a key role in controlling inhibitory neuronal activity. Modification of the efficacy of the synaptic strength is produced by changes in both the number of neuronal surface receptors and pentameric molecular assembly, leading to differences of sensitivity to neurotransmitters and neuromimetic drugs. Therefore, it is important to understand the molecular mechanisms regulating the so-called “life cycle of GABAA receptors” including sequential pentameric assembly at the site synthesized, intracellular transport through the Golgi apparatus and the cytoplasm, insertion into the cell membrane, functional modulation at the cell surface, and finally internalization, followed by either recycling back to the surface membrane or lysosomal degradation. This review is focused on events related to the surface expression of the receptor containing the γ2 subunit and clathrin/AP2 complex–mediated phospho-regulated endocytosis of the receptor, with special reference to the function of novel GABAA receptor modulators, GABARAP (GABAA receptor-associated protein) and PRIP (phospholipase C-related, but catalytically inactive protein). Keywords:: endocytosis, GABAA receptor, GABARAP (GABAA receptor-associated protein), PRIP (phospholipase C-related, but catalytically inactive protein), trafficking |
| first_indexed | 2024-12-11T15:03:52Z |
| format | Article |
| id | doaj.art-d6a713defb9243a886ce1cd0fa5f6c71 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T15:03:52Z |
| publishDate | 2007-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-d6a713defb9243a886ce1cd0fa5f6c712022-12-22T01:01:01ZengElsevierJournal of Pharmacological Sciences1347-86132007-01-011044285292Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein)Takashi Kanematsu0Akiko Mizokami1Keiko Watanabe2Masato Hirata3Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan; Corresponding author. inositol@dent.kyushu-u.ac.jpLaboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, JapanLaboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, JapanLaboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, JapanGABAA receptors are heteropentameric ligand-gated chloride channels composed of a variety of subunits, including α1 – 6, β1 – 3, γ1 – 3, δ, ε, θ, and π, and play a key role in controlling inhibitory neuronal activity. Modification of the efficacy of the synaptic strength is produced by changes in both the number of neuronal surface receptors and pentameric molecular assembly, leading to differences of sensitivity to neurotransmitters and neuromimetic drugs. Therefore, it is important to understand the molecular mechanisms regulating the so-called “life cycle of GABAA receptors” including sequential pentameric assembly at the site synthesized, intracellular transport through the Golgi apparatus and the cytoplasm, insertion into the cell membrane, functional modulation at the cell surface, and finally internalization, followed by either recycling back to the surface membrane or lysosomal degradation. This review is focused on events related to the surface expression of the receptor containing the γ2 subunit and clathrin/AP2 complex–mediated phospho-regulated endocytosis of the receptor, with special reference to the function of novel GABAA receptor modulators, GABARAP (GABAA receptor-associated protein) and PRIP (phospholipase C-related, but catalytically inactive protein). Keywords:: endocytosis, GABAA receptor, GABARAP (GABAA receptor-associated protein), PRIP (phospholipase C-related, but catalytically inactive protein), traffickinghttp://www.sciencedirect.com/science/article/pii/S1347861319342252 |
| spellingShingle | Takashi Kanematsu Akiko Mizokami Keiko Watanabe Masato Hirata Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) Journal of Pharmacological Sciences |
| title | Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) |
| title_full | Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) |
| title_fullStr | Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) |
| title_full_unstemmed | Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) |
| title_short | Regulation of GABAA-Receptor Surface Expression With Special Reference to the Involvement of GABARAP (GABAA Receptor-Associated Protein) and PRIP (Phospholipase C-Related, but Catalytically Inactive Protein) |
| title_sort | regulation of gabaa receptor surface expression with special reference to the involvement of gabarap gabaa receptor associated protein and prip phospholipase c related but catalytically inactive protein |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319342252 |
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