論文 - 詳細
| RRC ID | 75622 |
|---|---|
| 著者 | Kitakaze K, Ali H, Kimoto R, Takenouchi Y, Ishimaru H, Yamashita A, Ueda N, Tanaka T, Okamoto Y, Tsuboi K. |
| タイトル | GDE7 produces cyclic phosphatidic acid in the ER lumen functioning as a lysophospholipid mediator. |
| ジャーナル | Commun Biol |
| Abstract |
Cyclic phosphatidic acid (cPA) is a lipid mediator, which regulates adipogenic differentiation and glucose homeostasis by suppressing nuclear peroxisome proliferator-activated receptor γ (PPARγ). Glycerophosphodiesterase 7 (GDE7) is a Ca2+-dependent lysophospholipase D that localizes in the endoplasmic reticulum. Although mouse GDE7 catalyzes cPA production in a cell-free system, it is unknown whether GDE7 generates cPA in living cells. Here, we demonstrate that human GDE7 possesses cPA-producing activity in living cells as well as in a cell-free system. Furthermore, the active site of human GDE7 is directed towards the luminal side of the endoplasmic reticulum. Mutagenesis revealed that amino acid residues F227 and Y238 are important for catalytic activity. GDE7 suppresses the PPARγ pathway in human mammary MCF-7 and mouse preadipocyte 3T3-L1 cells, suggesting that cPA functions as an intracellular lipid mediator. These findings lead to a better understanding of the biological role of GDE7 and its product, cPA. |
| 巻・号 | 6(1) |
| ページ | 524 |
| 公開日 | 2023-5-16 |
| DOI | 10.1038/s42003-023-04900-4 |
| PII | 10.1038/s42003-023-04900-4 |
| PMID | 37193762 |
| PMC | PMC10188492 |
| MeSH | Animals Endoplasmic Reticulum / metabolism Humans Lysophospholipids / metabolism Mice PPAR gamma* / genetics PPAR gamma* / metabolism Phosphatidic Acids* / metabolism Phosphoric Diester Hydrolases / genetics |
| IF | 4.165 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |