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タイトル: Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation
著者: Suzuki, Eisuke
Ogawa, Namino
Takeda, Taka-Aki
Nishito, Yukina  KAKEN_id
Tanaka, Yu-Ki
Fujiwara, Takashi
Matsunaga, Mayu
Ueda, Sachiko
Kubo, Naoya
Tsuji, Tokuji
Fukunaka, Ayako
Yamazaki, Tomohiro
Taylor, Kathryn M
Ogra, Yasumitsu
Kambe, Taiho  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-9757-063X (unconfirmed)
著者名の別形: 鈴木, 英介
小川, 凡乃
武田, 貴成
西藤, 有希奈
松永, 麻佑
上田, 祥子
久保, 尚也
辻, 徳治
神戸, 大朋
発行日: 24-Apr-2020
出版者: American Society for Biochemistry and Molecular Biology(ASBMB)
誌名: Journal of Biological Chemistry
巻: 295
号: 17
開始ページ: 5669
終了ページ: 5684
抄録: Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.
著作権等: This research was originally published in the Journal of Biological Chemistry. [Eisuke Suzuki, Namino Ogawa, Taka-aki Takeda, Yukina Nishito, Yu-ki Tanaka, Takashi Fujiwara, Mayu Matsunaga, Sachiko Ueda, Naoya Kubo, Tokuji Tsuji, Ayako Fukunaka, Tomohiro Yamazaki, Kathryn M. Taylor, Yasumitsu Ogra, Taiho Kambe. Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation. 'Journal of biological chemistry' 2020; 295; 5669-5684. © 2020 Suzuki et al.
The full-text file will be made open to the public on 24 April 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'
URI: http://hdl.handle.net/2433/251413
DOI(出版社版): 10.1074/jbc.RA120.012610
PubMed ID: 32179649
出現コレクション:学術雑誌掲載論文等

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