The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice
The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifical...
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| Veröffentlicht in: | The Journal of biological chemistry 2003-08, Vol.278 (35), p.33474-33481 |
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| creator | Dufner-Beattie, Jodi Wang, Fudi Kuo, Yien-Ming Gitschier, Jane Eide, David Andrews, Glen K. |
| description | The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. These results provide compelling evidence that ZIP4 is a zinc transporter that plays an important role in zinc homeostasis, a process that is defective in acrodermatitis enteropathica in humans. |
| doi_str_mv | 10.1074/jbc.M305000200 |
| format | Article |
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To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. These results provide compelling evidence that ZIP4 is a zinc transporter that plays an important role in zinc homeostasis, a process that is defective in acrodermatitis enteropathica in humans.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M305000200</identifier><identifier>PMID: 12801924</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acrodermatitis - metabolism ; Amino Acid Sequence ; Animals ; Biological Transport ; Blotting, Northern ; Carrier Proteins - metabolism ; Cation Transport Proteins - chemistry ; Cation Transport Proteins - metabolism ; Cation Transport Proteins - physiology ; Cations ; Cell Membrane - metabolism ; Dose-Response Relationship, Drug ; Female ; Immunohistochemistry ; Intestinal Mucosa - metabolism ; Intestine, Small - embryology ; Kinetics ; Male ; Metals - chemistry ; Mice ; Models, Genetic ; Molecular Sequence Data ; Peptides - chemistry ; Plasmids - metabolism ; Protein Structure, Tertiary ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - metabolism ; RNA, Messenger - metabolism ; Sequence Homology, Amino Acid ; Tissue Distribution ; Transfection ; Zinc - metabolism</subject><ispartof>The Journal of biological chemistry, 2003-08, Vol.278 (35), p.33474-33481</ispartof><rights>2003 © 2003 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-ae5f8954020cdcaef837de76eefd083bb29d881a135f1ab8f15e57a510aff7613</citedby><cites>FETCH-LOGICAL-c551t-ae5f8954020cdcaef837de76eefd083bb29d881a135f1ab8f15e57a510aff7613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12801924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dufner-Beattie, Jodi</creatorcontrib><creatorcontrib>Wang, Fudi</creatorcontrib><creatorcontrib>Kuo, Yien-Ming</creatorcontrib><creatorcontrib>Gitschier, Jane</creatorcontrib><creatorcontrib>Eide, David</creatorcontrib><creatorcontrib>Andrews, Glen K.</creatorcontrib><title>The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. These results provide compelling evidence that ZIP4 is a zinc transporter that plays an important role in zinc homeostasis, a process that is defective in acrodermatitis enteropathica in humans.</description><subject>Acrodermatitis - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Blotting, Northern</subject><subject>Carrier Proteins - metabolism</subject><subject>Cation Transport Proteins - chemistry</subject><subject>Cation Transport Proteins - metabolism</subject><subject>Cation Transport Proteins - physiology</subject><subject>Cations</subject><subject>Cell Membrane - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Immunohistochemistry</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestine, Small - embryology</subject><subject>Kinetics</subject><subject>Male</subject><subject>Metals - chemistry</subject><subject>Mice</subject><subject>Models, Genetic</subject><subject>Molecular Sequence Data</subject><subject>Peptides - chemistry</subject><subject>Plasmids - metabolism</subject><subject>Protein Structure, Tertiary</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Tissue Distribution</subject><subject>Transfection</subject><subject>Zinc - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1r3DAQhkVoabZprzkWHUpO9UZjWbF8DEuaBhLawwZKLkKWRvGE9UclO6X_vkp3IaeehhmeeZl5GDsFsQZRV-dPrVvfSaGEEKUQR2wFQstCKvj5hq3yDIqmVPqYvU_pKTOiauAdO4ZSC2jKasX6bYf80sXRY-ztTDMlfjXMGMfJzh05y69xQP5w86PKc5exxC3fUkoLFmlCR4HcF_5AgysiPi47O6P_1_JttEOaxpjDOA38jhx-YG-D3SX8eKgn7P7r1Xbzrbj9fn2zubwtnFIwFxZV0I2q8kvOO4tBy9pjfYEYfH6vbcvGaw0WpApgWx1AoaqtAmFDqC9AnrCzfe4Ux18Lptn0lBzudnbAcUkGtBZ1KWUG13swG0gpYjBTpN7GPwaEeRFssmDzKjgvfDokL22P_hU_GM3A5z3Q0WP3myKalkbXYW_KWhupjJRV_YLpPYZZwzNhNMkRDg59XnGz8SP974S_CxaVyA</recordid><startdate>20030829</startdate><enddate>20030829</enddate><creator>Dufner-Beattie, Jodi</creator><creator>Wang, Fudi</creator><creator>Kuo, Yien-Ming</creator><creator>Gitschier, Jane</creator><creator>Eide, David</creator><creator>Andrews, Glen K.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20030829</creationdate><title>The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice</title><author>Dufner-Beattie, Jodi ; Wang, Fudi ; Kuo, Yien-Ming ; Gitschier, Jane ; Eide, David ; Andrews, Glen K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-ae5f8954020cdcaef837de76eefd083bb29d881a135f1ab8f15e57a510aff7613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acrodermatitis - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Blotting, Northern</topic><topic>Carrier Proteins - metabolism</topic><topic>Cation Transport Proteins - chemistry</topic><topic>Cation Transport Proteins - metabolism</topic><topic>Cation Transport Proteins - physiology</topic><topic>Cations</topic><topic>Cell Membrane - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Immunohistochemistry</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestine, Small - embryology</topic><topic>Kinetics</topic><topic>Male</topic><topic>Metals - chemistry</topic><topic>Mice</topic><topic>Models, Genetic</topic><topic>Molecular Sequence Data</topic><topic>Peptides - chemistry</topic><topic>Plasmids - metabolism</topic><topic>Protein Structure, Tertiary</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Tissue Distribution</topic><topic>Transfection</topic><topic>Zinc - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dufner-Beattie, Jodi</creatorcontrib><creatorcontrib>Wang, Fudi</creatorcontrib><creatorcontrib>Kuo, Yien-Ming</creatorcontrib><creatorcontrib>Gitschier, Jane</creatorcontrib><creatorcontrib>Eide, David</creatorcontrib><creatorcontrib>Andrews, Glen K.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dufner-Beattie, Jodi</au><au>Wang, Fudi</au><au>Kuo, Yien-Ming</au><au>Gitschier, Jane</au><au>Eide, David</au><au>Andrews, Glen K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2003-08-29</date><risdate>2003</risdate><volume>278</volume><issue>35</issue><spage>33474</spage><epage>33481</epage><pages>33474-33481</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. 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| subjects | Acrodermatitis - metabolism Amino Acid Sequence Animals Biological Transport Blotting, Northern Carrier Proteins - metabolism Cation Transport Proteins - chemistry Cation Transport Proteins - metabolism Cation Transport Proteins - physiology Cations Cell Membrane - metabolism Dose-Response Relationship, Drug Female Immunohistochemistry Intestinal Mucosa - metabolism Intestine, Small - embryology Kinetics Male Metals - chemistry Mice Models, Genetic Molecular Sequence Data Peptides - chemistry Plasmids - metabolism Protein Structure, Tertiary Reverse Transcriptase Polymerase Chain Reaction RNA - metabolism RNA, Messenger - metabolism Sequence Homology, Amino Acid Tissue Distribution Transfection Zinc - metabolism |
| title | The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice |
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