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タイトル: | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
著者: | Wagatsuma, Takumi Shimotsuma, Keiko Sogo, Akiko Sato, Risa Kubo, Naoya Ueda, Sachiko Uchida, Yasuo Kinoshita, Masato https://orcid.org/0000-0003-3936-7371 (unconfirmed) Kambe, Taiho https://orcid.org/0000-0001-9757-063X (unconfirmed) |
著者名の別形: | 我妻, 拓実 下間, 敬子 十河, 暁子 久保, 尚也 上田, 祥子 木下, 政人 神戸, 大朋 |
キーワード: | zinc glycosylphosphatidylinositol (GPI anchor) transporter cell surface ER quality control ZNT early secretory pathway ectoenzyme phosphatidylinositol glycan anchor biosynthesis (PIG) |
発行日: | Jun-2022 |
出版者: | Elsevier BV American Society for Biochemistry and Molecular Biology |
誌名: | Journal of Biological Chemistry |
巻: | 298 |
号: | 6 |
論文番号: | 102011 |
抄録: | Glycosylphosphatidylinositol (GPI)-anchored proteins play crucial roles in various enzyme activities, cell signaling and adhesion, and immune responses. While the molecular mechanism underlying GPI-anchored protein biosynthesis has been well studied, the role of zinc transport in this process has not yet been elucidated. Zn transporter (ZNT) proteins mobilize cytosolic zinc to the extracellular space and to intracellular compartments. Here, we report that the early secretory pathway ZNTs [ZNT5-ZNT6 heterodimers (ZNT5-6) and ZNT7-ZNT7 homodimers (ZNT7)], which supply zinc to the lumen of the early secretory pathway compartments are essential for GPI-anchored protein expression on the cell surface. We show, using overexpression and gene disruption/re-expression strategies in cultured human cells, that loss of ZNT5-6 and ZNT7 zinc transport functions results in significant reduction in GPI-anchored protein levels similar to that in mutant cells lacking phosphatidylinositol glycan anchor biosynthesis (PIG) genes. Furthermore, medaka fish with disrupted Znt5 and Znt7 genes show touch-insensitive phenotypes similar to zebrafish Pig mutants. These findings provide a previously unappreciated insight into the regulation of GPI-anchored protein expression and protein quality control in the early secretory pathway. |
著作権等: | © 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the Creative Commons Attribution 4.0 International license |
URI: | http://hdl.handle.net/2433/276852 |
DOI(出版社版): | 10.1016/j.jbc.2022.102011 |
PubMed ID: | 35525268 |
出現コレクション: | 学術雑誌掲載論文等 |
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