TY - JOUR
T1 - Characterization of the GufA subfamily member SLC39A11/Zip11 as a zinc transporter
AU - Yu, Yu
AU - Wu, Aimin
AU - Zhang, Zhuzhen
AU - Yan, Guang
AU - Zhang, Fan
AU - Zhang, Lihong
AU - Shen, Xiaoyun
AU - Hu, Ronggui
AU - Zhang, Yan
AU - Zhang, Keying
AU - Wang, Fudi
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China grants (No. 31225013 and 31030039 to F.W., 30901193 to Y.Y., 81100943 to L.Z.); Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition (grant number 11DZ2260500); China Postdoctoral Science Foundation (No. 2012M510902 to Y.Y.) and SIBS-CAS Outstanding Youth Fellowship (No. 2010KIP309 to Y.Y.). This work is also supported by Distinguished Professorship Program from Zhejiang University to F.W. We appreciate the encouragement and helpful comments from other members of the Wang laboratory.
PY - 2013/10
Y1 - 2013/10
N2 - Cellular zinc influx and efflux are maintained by two major transporter families, the ZIP (SLC39A) and ZnT (SLC30A or CDF) molecules. The functions of one molecule in this class, ZIP11/SLC39A11, remain unclear. Bioinformatics analysis of the distribution and evolutionary relationships of different ZIP members in eukaryotes and prokaryotes indicated that Zip11, the sole member of gufA subfamily, is an ancient ZIP family member that might have originated in early eukaryotic ancestors. Murine Zip11 mRNA is abundantly expressed in testes and the digestive system including stomach, ileum and cecum. Analysis of cellular zinc content, metallothionein levels, and cell viability under high or low zinc conditions in cells transfected with a murine Zip11 expression plasmid, suggest that Zip11 is a zinc importer. Further, cellular zinc concentrations and metallothionein levels decreased when Zip11 was knocked down. In mice supplemented with zinc, both mRNA and protein levels of Zip11 were slightly up-regulated in several tissues. The metal response element sequences (MREs) upstream of the first exon of Zip11 responded to elevated extracellular zinc concentrations, as assessed by luciferase reporter assays. Mutagenic analysis showed that several of the MREs could regulate Zip11 promoter activity, and metal-responsive transcription factor-1 (MTF-1) was shown to be involved in this process. Collectively, these data suggest that Zip11 has unique protein sequence and structure features, it functions as a cellular zinc transporter, and its expression is at least partially regulated by zinc via hMTF-1 binding to MREs of the Zip11 promoter.
AB - Cellular zinc influx and efflux are maintained by two major transporter families, the ZIP (SLC39A) and ZnT (SLC30A or CDF) molecules. The functions of one molecule in this class, ZIP11/SLC39A11, remain unclear. Bioinformatics analysis of the distribution and evolutionary relationships of different ZIP members in eukaryotes and prokaryotes indicated that Zip11, the sole member of gufA subfamily, is an ancient ZIP family member that might have originated in early eukaryotic ancestors. Murine Zip11 mRNA is abundantly expressed in testes and the digestive system including stomach, ileum and cecum. Analysis of cellular zinc content, metallothionein levels, and cell viability under high or low zinc conditions in cells transfected with a murine Zip11 expression plasmid, suggest that Zip11 is a zinc importer. Further, cellular zinc concentrations and metallothionein levels decreased when Zip11 was knocked down. In mice supplemented with zinc, both mRNA and protein levels of Zip11 were slightly up-regulated in several tissues. The metal response element sequences (MREs) upstream of the first exon of Zip11 responded to elevated extracellular zinc concentrations, as assessed by luciferase reporter assays. Mutagenic analysis showed that several of the MREs could regulate Zip11 promoter activity, and metal-responsive transcription factor-1 (MTF-1) was shown to be involved in this process. Collectively, these data suggest that Zip11 has unique protein sequence and structure features, it functions as a cellular zinc transporter, and its expression is at least partially regulated by zinc via hMTF-1 binding to MREs of the Zip11 promoter.
KW - MRE
KW - MTF-1
KW - SLC39A11/ZIP11
KW - ZIP family
KW - Zinc homeostasis
KW - Zinc transporter
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U2 - 10.1016/j.jnutbio.2013.02.010
DO - 10.1016/j.jnutbio.2013.02.010
M3 - Article
C2 - 23643525
AN - SCOPUS:84883765503
SN - 0955-2863
VL - 24
SP - 1697
EP - 1708
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
IS - 10
ER -