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Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression
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 no...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168625/ https://www.ncbi.nlm.nih.gov/pubmed/35525268 http://dx.doi.org/10.1016/j.jbc.2022.102011 |
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author | Wagatsuma, Takumi Shimotsuma, Keiko Sogo, Akiko Sato, Risa Kubo, Naoya Ueda, Sachiko Uchida, Yasuo Kinoshita, Masato Kambe, Taiho |
author_facet | Wagatsuma, Takumi Shimotsuma, Keiko Sogo, Akiko Sato, Risa Kubo, Naoya Ueda, Sachiko Uchida, Yasuo Kinoshita, Masato Kambe, Taiho |
author_sort | Wagatsuma, Takumi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9168625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-91686252022-06-08 Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression Wagatsuma, Takumi Shimotsuma, Keiko Sogo, Akiko Sato, Risa Kubo, Naoya Ueda, Sachiko Uchida, Yasuo Kinoshita, Masato Kambe, Taiho J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2022-05-04 /pmc/articles/PMC9168625/ /pubmed/35525268 http://dx.doi.org/10.1016/j.jbc.2022.102011 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Wagatsuma, Takumi Shimotsuma, Keiko Sogo, Akiko Sato, Risa Kubo, Naoya Ueda, Sachiko Uchida, Yasuo Kinoshita, Masato Kambe, Taiho Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title_full | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title_fullStr | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title_full_unstemmed | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title_short | Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
title_sort | zinc transport via znt5-6 and znt7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168625/ https://www.ncbi.nlm.nih.gov/pubmed/35525268 http://dx.doi.org/10.1016/j.jbc.2022.102011 |
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