Originally published In Press as doi:10.1074/jbc.M305000200 on June 11, 2003
J. Biol. Chem., Vol. 278, Issue 35, 33474-33481, August 29, 2003
The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice*
Jodi Dufner-Beattie 
,
Fudi Wang 
,
Yien-Ming Kuo ¶,
Jane Gitschier ¶,
David Eide and
Glen K. Andrews ||
From the
Department of Biochemistry and Molecular
Biology, University of Kansas Medical Center, Kansas City, Kansas 66160-7421,
the Departments of Nutritional Sciences and
Biochemistry, University of Missouri, Columbia, Missouri 65211, and the
¶Howard Hughes Medical Institute and Departments
of Medicine and Pediatrics, University of California, San Francisco,
California 94143
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.
Received for publication, May 13, 2003
, and in revised form, June 10, 2003.
* This work was supported in part by National Institutes of Health Grants
DK063975 (to G. K. A.) and GM56285 (to D. E.) and by pilot project funds from
the University of Kansas Research Institute. The costs of publication of this
article were defrayed in part by the payment of page charges. This article
must therefore be hereby marked "advertisement"in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
||
To whom correspondence should be addressed: Dept. of Biochemistry and
Molecular Biology, Mail Stop 3030, University of Kansas Medical Center, 39th
and Rainbow Blvd., Kansas City, KS 66160-7421. Tel.: 913-588-6935; Fax:
913-588-2711; E-mail:
gandrews{at}kumc.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Zheng, G. P. Feeney, P. Kille, and C. Hogstrand
Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc repression of ZIP10 transcription by an intronic MRE cluster
Physiol Genomics,
July 9, 2008;
34(2):
205 - 214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Girijashanker, L. He, M. Soleimani, J. M. Reed, H. Li, Z. Liu, B. Wang, T. P. Dalton, and D. W. Nebert
Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter
Mol. Pharmacol.,
May 1, 2008;
73(5):
1413 - 1423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kambe, J. Geiser, B. Lahner, D. E. Salt, and G. K. Andrews
Slc39a1 to 3 (subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency
Am J Physiol Regulatory Integrative Comp Physiol,
May 1, 2008;
294(5):
R1474 - R1481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Dainty, C. A. Kennedy, S. Watt, J. Bahler, and S. K. Whitehall
Response of Schizosaccharomyces pombe to Zinc Deficiency
Eukaryot. Cell,
March 1, 2008;
7(3):
454 - 464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Goodstadt, A. Heger, C. Webber, and C. P. Ponting
An analysis of the gene complement of a marsupial, Monodelphis domestica: Evolution of lineage-specific genes and giant chromosomes
Genome Res.,
July 1, 2007;
17(7):
969 - 981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dufner-Beattie, B. P. Weaver, J. Geiser, M. Bilgen, M. Larson, W. Xu, and G. K. Andrews
The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency
Hum. Mol. Genet.,
June 15, 2007;
16(12):
1391 - 1399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Jamieson, J. N. Shuhyta, and C. G. Taylor
Lead Does Not Affect Transcription of Intestinal Zinc-Binding Proteins in Growing Rats
Experimental Biology and Medicine,
June 1, 2007;
232(6):
744 - 753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Jackson, R. M. Helston, J. A. McKay, E. D. O'Neill, J. C. Mathers, and D. Ford
Splice Variants of the Human Zinc Transporter ZnT5 (SLC30A5) Are Differentially Localized and Regulated by Zinc through Transcription and mRNA Stability
J. Biol. Chem.,
April 6, 2007;
282(14):
10423 - 10431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Mao, B.-E. Kim, F. Wang, D. J. Eide, and M. J. Petris
A Histidine-rich Cluster Mediates the Ubiquitination and Degradation of the Human Zinc Transporter, hZIP4, and Protects against Zinc Cytotoxicity
J. Biol. Chem.,
March 9, 2007;
282(10):
6992 - 7000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P Bressler, L. Olivi, J. H. Cheong, Y. Kim, A. Maerten, and D. Bannon
Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities
Human and Experimental Toxicology,
March 1, 2007;
26(3):
221 - 229.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y. Y. Yu, C. P. Kirschke, and L. Huang
Immunohistochemical Analysis of ZnT1, 4, 5, 6, and 7 in the Mouse Gastrointestinal Tract
J. Histochem. Cytochem.,
March 1, 2007;
55(3):
223 - 234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Kaler and R. Prasad
Molecular cloning and functional characterization of novel zinc transporter rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane
Am J Physiol Renal Physiol,
January 1, 2007;
292(1):
F217 - F229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yepiskoposyan, D. Egli, T. Fergestad, A. Selvaraj, C. Treiber, G. Multhaup, O. Georgiev, and W. Schaffner
Transcriptome response to heavy metal stress in Drosophila reveals a new zinc transporter that confers resistance to zinc
Nucleic Acids Res.,
October 18, 2006;
34(17):
4866 - 4877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Liuzzi, F. Aydemir, H. Nam, M. D. Knutson, and R. J. Cousins
Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells
PNAS,
September 12, 2006;
103(37):
13612 - 13617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Cousins, J. P. Liuzzi, and L. A. Lichten
Mammalian Zinc Transport, Trafficking, and Signals
J. Biol. Chem.,
August 25, 2006;
281(34):
24085 - 24089.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dufner-Beattie, Z. L. Huang, J. Geiser, W. Xu, and G. K. Andrews
Generation and Characterization of Mice Lacking the Zinc Uptake Transporter ZIP3
Mol. Cell. Biol.,
July 1, 2005;
25(13):
5607 - 5615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Chowanadisai, S. L. Kelleher, and B. Lonnerdal
Zinc Deficiency Is Associated with Increased Brain Zinc Import and LIV-1 Expression and Decreased ZnT-1 Expression in Neonatal Rats
J. Nutr.,
May 1, 2005;
135(5):
1002 - 1007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R A Cragg, S R Phillips, J M Piper, J S Varma, F C Campbell, J C Mathers, and D Ford
Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation
Gut,
April 1, 2005;
54(4):
469 - 478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. P. Dalton, L. He, B. Wang, M. L. Miller, L. Jin, K. F. Stringer, X. Chang, C. S. Baxter, and D. W. Nebert
Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis
PNAS,
March 1, 2005;
102(9):
3401 - 3406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Mathews, F. Wang, D. J. Eide, and M. Van Doren
Drosophila fear of intimacy Encodes a Zrt/IRT-like Protein (ZIP) Family Zinc Transporter Functionally Related to Mammalian ZIP Proteins
J. Biol. Chem.,
January 7, 2005;
280(1):
787 - 795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Wang, B.-E. Kim, M. J. Petris, and D. J. Eide
The Mammalian Zip5 Protein Is a Zinc Transporter That Localizes to the Basolateral Surface of Polarized Cells
J. Biol. Chem.,
December 3, 2004;
279(49):
51433 - 51441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dufner-Beattie, Y.-M. Kuo, J. Gitschier, and G. K. Andrews
The Adaptive Response to Dietary Zinc in Mice Involves the Differential Cellular Localization and Zinc Regulation of the Zinc Transporters ZIP4 and ZIP5
J. Biol. Chem.,
November 19, 2004;
279(47):
49082 - 49090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Liuzzi, J. A. Bobo, L. A. Lichten, D. A. Samuelson, and R. J. Cousins
Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis
PNAS,
October 5, 2004;
101(40):
14355 - 14360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Wang, J. Dufner-Beattie, B.-E. Kim, M. J. Petris, G. Andrews, and D. J. Eide
Zinc-stimulated Endocytosis Controls Activity of the Mouse ZIP1 and ZIP3 Zinc Uptake Transporters
J. Biol. Chem.,
June 4, 2004;
279(23):
24631 - 24639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kordas and R. J. Stoltzfus
New Evidence of Iron and Zinc Interplay at the Enterocyte and Neural Tissues
J. Nutr.,
June 1, 2004;
134(6):
1295 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Wang, B.-E. Kim, J. Dufner-Beattie, M. J. Petris, G. Andrews, and D. J. Eide
Acrodermatitis enteropathica mutations affect transport activity, localization and zinc-responsive trafficking of the mouse ZIP4 zinc transporter
Hum. Mol. Genet.,
March 1, 2004;
13(5):
563 - 571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B.-E. Kim, F. Wang, J. Dufner-Beattie, G. K. Andrews, D. J. Eide, and M. J. Petris
Zn2+-stimulated Endocytosis of the mZIP4 Zinc Transporter Regulates Its Location at the Plasma Membrane
J. Biol. Chem.,
February 6, 2004;
279(6):
4523 - 4530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Rutherford and A. J. Bird
Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells
Eukaryot. Cell,
February 1, 2004;
3(1):
1 - 13.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dufner-Beattie, S. J. Langmade, F. Wang, D. Eide, and G. K. Andrews
Structure, Function, and Regulation of a Subfamily of Mouse Zinc Transporter Genes
J. Biol. Chem.,
December 12, 2003;
278(50):
50142 - 50150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L Kelleher and B. Lonnerdal
Zn Transporter Levels and Localization Change Throughout Lactation in Rat Mammary Gland and Are Regulated by Zn in Mammary Cells
J. Nutr.,
November 1, 2003;
133(11):
3378 - 3385.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
