The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis
Abstract The essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal‐responsive transcriptional regulators are linked to zinc homeostasis. However, the mec...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406421 |
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| author | Shumin Sun Enjun Xie Shan Xu Suyu Ji Shufen Wang Jie Shen Rong Wang Xinyi Shen Yunxing Su Zijun Song Xiaotian Wu Jiahui Zhou Zhaoxian Cai Xiaopeng Li Yan Zhang Junxia Min Fudi Wang |
| author_facet | Shumin Sun Enjun Xie Shan Xu Suyu Ji Shufen Wang Jie Shen Rong Wang Xinyi Shen Yunxing Su Zijun Song Xiaotian Wu Jiahui Zhou Zhaoxian Cai Xiaopeng Li Yan Zhang Junxia Min Fudi Wang |
| author_sort | Shumin Sun |
| collection | DOAJ |
| description | Abstract The essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal‐responsive transcriptional regulators are linked to zinc homeostasis. However, the mechanism underlying the regulation of systemic zinc homeostasis remains largely unknown. Here, it is reported that the intestinal transporter SLC30A1 plays an essential role in maintaining systemic zinc homeostasis. Using several lines of tissue‐specific knockout mice, it is found that intestinal Slc30a1 plays a critical role in survival. Furthermore, lineage tracing reveals that Slc30a1 is localized to the basolateral membrane of intestinal epithelial cells (IECs). It is also found that Slc30a1 safeguards both intestinal barrier integrity and systemic zinc homeostasis. Finally, an integrative analysis of the cryo‐EM structure and site‐specific mutagenesis of human SLC30A1 are performed and a zinc transport mechanism of SLC30A1 unique within the SLC30A family, with His43 serving as a critical residue for zinc selectivity, is identified. |
| format | Article |
| id | doaj-art-d87f2168c8a246e2b8d0da314522991b |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d87f2168c8a246e2b8d0da314522991b2025-08-20T01:59:00ZengWileyAdvanced Science2198-38442024-12-011146n/an/a10.1002/advs.202406421The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc HomeostasisShumin Sun0Enjun Xie1Shan Xu2Suyu Ji3Shufen Wang4Jie Shen5Rong Wang6Xinyi Shen7Yunxing Su8Zijun Song9Xiaotian Wu10Jiahui Zhou11Zhaoxian Cai12Xiaopeng Li13Yan Zhang14Junxia Min15Fudi Wang16The First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Biophysics and Department of Pathology Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe First Affiliated Hospital Basic Medical Sciences School of Public Health Hengyang Medical School University of South China Hengyang 421001 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Biophysics and Department of Pathology Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University School of Medicine Hangzhou 310058 ChinaThe Second Affiliated Hospital School of Public Health Zhejiang University School of Medicine Hangzhou 310058 ChinaAbstract The essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal‐responsive transcriptional regulators are linked to zinc homeostasis. However, the mechanism underlying the regulation of systemic zinc homeostasis remains largely unknown. Here, it is reported that the intestinal transporter SLC30A1 plays an essential role in maintaining systemic zinc homeostasis. Using several lines of tissue‐specific knockout mice, it is found that intestinal Slc30a1 plays a critical role in survival. Furthermore, lineage tracing reveals that Slc30a1 is localized to the basolateral membrane of intestinal epithelial cells (IECs). It is also found that Slc30a1 safeguards both intestinal barrier integrity and systemic zinc homeostasis. Finally, an integrative analysis of the cryo‐EM structure and site‐specific mutagenesis of human SLC30A1 are performed and a zinc transport mechanism of SLC30A1 unique within the SLC30A family, with His43 serving as a critical residue for zinc selectivity, is identified.https://doi.org/10.1002/advs.202406421intestinal barrier integrityion selectivitySLC30A1 structurezinc homeostasis |
| spellingShingle | Shumin Sun Enjun Xie Shan Xu Suyu Ji Shufen Wang Jie Shen Rong Wang Xinyi Shen Yunxing Su Zijun Song Xiaotian Wu Jiahui Zhou Zhaoxian Cai Xiaopeng Li Yan Zhang Junxia Min Fudi Wang The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis Advanced Science intestinal barrier integrity ion selectivity SLC30A1 structure zinc homeostasis |
| title | The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis |
| title_full | The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis |
| title_fullStr | The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis |
| title_full_unstemmed | The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis |
| title_short | The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis |
| title_sort | intestinal transporter slc30a1 plays a critical role in regulating systemic zinc homeostasis |
| topic | intestinal barrier integrity ion selectivity SLC30A1 structure zinc homeostasis |
| url | https://doi.org/10.1002/advs.202406421 |
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