Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant

PLoS ONE

Volumn 8, Issue 5, 2013, Pages

  Itsumura, Naoya ^a   Inamo, Yasuji ^b   Okazaki, Fumiko ^c   Teranishi, Fumie ^a   Narita, Hiroshi ^c   Kambe, Taiho ^a   Kodama, Hiroko ^d,e  

^a KYOTO UNIVERSITY   (Japan)

^b NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c KYOTO WOMEN'S UNIVERSITY   (Japan)

^d TEIKYO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^e TEIKYO HEISEI UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

LEUCINE; SERINE; ZINC;

ALLELE; ANIMAL CELL; ARTICLE; B LYMPHOCYTE; BREAST FEEDING; BREAST MILK; CASE REPORT; CHICKEN; COMPLEX FORMATION; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISEASE SEVERITY; EXON; FEMALE; GENE; GENE SEQUENCE; GENETIC TRANSFECTION; GENOTYPE; HETEROZYGOSITY; HUMAN; IMMUNOBLOTTING; IMMUNOPRECIPITATION; INFANT; JAPANESE; MALE; MISSENSE MUTATION; MOTHER; NONHUMAN; NUCLEOTIDE SEQUENCE; PLASMID; SEQUENCE ALIGNMENT; SLC30A2 GENE; ZINC DEFICIENCY; ZNT2 GENE;

AMINO ACID SEQUENCE; ANIMALS; ASIAN CONTINENTAL ANCESTRY GROUP; B-LYMPHOCYTES; BASE SEQUENCE; BREAST FEEDING; CATION TRANSPORT PROTEINS; CATIONS, DIVALENT; CELL LINE; CHICKENS; EXONS; FEMALE; HETEROZYGOTE; HUMANS; INFANT; ION TRANSPORT; LACTATION; METAL METABOLISM, INBORN ERRORS; MILK, HUMAN; MOLECULAR SEQUENCE DATA; MUTATION; ZINC;

EID: 84878579262     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0064045     Document Type: Article

References (68)

1. Vallee BL, Falchuk KH, (1993) The biochemical basis of zinc physiology. Physiol Rev 73: 79-118.
2. Maret W, Li Y, (2009) Coordination dynamics of zinc in proteins. Chem Rev 109: 4682-4707.
3. Fukada T, Kambe T, (2011) Molecular and genetic features of zinc transporters in physiology and pathogenesis. Metallomics 3: 662-674.
4. Prasad AS, (1995) Zinc: An overview. Nutrition 11: 93-99.
5. Hambidge M, (2000) Human zinc deficiency. J Nutr 130: 1344S-1349S.
6. Kambe T, Weaver BP, Andrews GK, (2008) The genetics of essential metal homeostasis during development. Genesis 46: 214-228.
7. Aggett PJ, Atherton DJ, More J, Davey J, Delves HT, et al. (1980) Symptomatic zinc deficiency in a breast-fed preterm infant. Arch Dis Child 55: 547-550.
8. Zimmerman AW, Hambidge KM, Lepow ML, Greenberg RD, Stover ML, et al. (1982) Acrodermatitis in breast-fed premature infants: Evidence for a defect of mammary zinc secretion. Pediatrics 69: 176-183.
9. Kiechl-Kohlendorfer U, Fink FM, Steichen-Gersdorf E, (2007) Transient symptomatic zinc deficiency in a breast-fed preterm infant. Pediatr Dermatol 24: 536-540.
10. Barbarot S, Chantier E, Kuster A, Hello M, Roze JC, et al. (2010) Symptomatic acquired zinc deficiency in at-risk premature infants: High dose preventive supplementation is necessary. Pediatr Dermatol 27: 380-383.
11. Kienast A, Roth B, Bossier C, Hojabri C, Hoeger PH, (2007) Zinc-deficiency dermatitis in breast-fed infants. Eur J Pediatr 166: 189-194.
12. Krieger I, Alpern BE, Cunnane SC, (1986) Transient neonatal zinc deficiency. Am J Clin Nutr 43: 955-958.
13. Roberts LJ, Shadwick CF, Bergstresser PR, (1987) Zinc deficiency in two full-term breast-fed infants. J Am Acad Dermatol 16: 301-304.
14. Chowanadisai W, Lonnerdal B, Kelleher SL, (2006) Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J Biol Chem 281: 39699-39707.
15. Murthy SC, Udagani MM, Badakali AV, Yelameli BC, (2010) Symptomatic zinc deficiency in a full-term breast-fed infant. Dermatol Online J 16: 3.
16. Park CH, Lee MJ, Kim HJ, Lee G, Park JW, et al. (2010) Congenital zinc deficiency from mutations of the SLC39A4 gene as the genetic background of acrodermatitis enteropathica. J Korean Med Sci 25: 1818-1820.
17. Lasry I, Seo YA, Ityel H, Shalva N, Pode-Shakked B, et al. (2012) A dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency. J Biol Chem 287: 29348-29361.
18. Wang F, Kim BE, Dufner-Beattie J, Petris MJ, Andrews G, et al. (2004) Acrodermatitis enteropathica mutations affect transport activity, localization and zinc-responsive trafficking of the mouse ZIP4 zinc transporter. Hum Mol Genet 13: 563-571.
19. Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, et al. (2002) Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31: 239-240.
20. Andrews GK, (2008) Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem Soc Trans 36: 1242-1246.
21. Kambe T, Andrews GK, (2009) Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations. Mol Cell Biol 29: 129-139.
22. Ackland ML, Michalczyk A, (2006) Zinc deficiency and its inherited disorders-a review. Genes Nutr 1: 41-49.
23. Huang L, Gitschier J, (1997) A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17: 292-297.
24. Suzuki T, Ishihara K, Migaki H, Matsuura W, Kohda A, et al. (2005) Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane. J Biol Chem 280: 637-643.
25. Suzuki T, Ishihara K, Migaki H, Nagao M, Yamaguchi-Iwai Y, et al. (2005) Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells. J Biol Chem 280: 30956-30962.
26. Ishihara K, Yamazaki T, Ishida Y, Suzuki T, Oda K, et al. (2006) Zinc transport complexes contribute to the homeostatic maintenance of secretory pathway function in vertebrate cells. J Biol Chem 281: 17743-17750.
27. Matsuura W, Yamazaki T, Yamaguchi-Iwai Y, Masuda S, Nagao M, et al. (2009) SLC39A9 (ZIP9) regulates zinc homeostasis in the secretory pathway: Characterization of the ZIP subfamily I protein in vertebrate cells. Biosci Biotechnol Biochem 73: 1142-1148.
28. Fukunaka A, Suzuki T, Kurokawa Y, Yamazaki T, Fujiwara N, et al. (2009) Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in the early secretory pathway. J Biol Chem 284: 30798-30806.
29. Fukunaka A, Kurokawa Y, Teranishi F, Sekler I, Oda K, et al. (2011) Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. J Biol Chem 286: 16363-16373.
30. Krebs NF, Reidinger CJ, Hartley S, Robertson AD, Hambidge KM, (1995) Zinc supplementation during lactation: Effects on maternal status and milk zinc concentrations. Am J Clin Nutr 61: 1030-1036.
31. Dorea JG, (2002) Zinc deficiency in nursing infants. J Am.Coll Nutr 21: 84-87.
32. Buerstedde JM, Takeda S, (1991) Increased ratio of targeted to random integration after transfection of chicken B cell lines. Cell 67: 179-188.
33. Kambe T, Narita H, Yamaguchi-Iwai Y, Hirose J, Amano T, et al. (2002) Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells. J Biol Chem 277: 19049-19055.
34. Michalczyk A, Varigos G, Catto-Smith A, Blomeley RC, Ackland ML, (2003) Analysis of zinc transporter, hZnT4 (Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk. Hum Genet 113: 202-210.
35. Guo L, Lichten LA, Ryu MS, Liuzzi JP, Wang F, et al. (2010) STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of ZnT2 (Slc30a2) in pancreatic acinar cells. Proc Natl Acad Sci U S A 107: 2818-2823.
36. Liuzzi JP, Bobo JA, Lichten LA, Samuelson DA, Cousins RJ, (2004) Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis. Proc Natl Acad Sci U S A 101: 14355-14360.
37. Qian L, Lopez V, Seo YA, Kelleher SL, (2009) Prolactin regulates ZNT2 expression through the JAK2/STAT5 signaling pathway in mammary cells. Am J Physiol Cell Physiol 297: C369-377.
38. McCormick N, Velasquez V, Finney L, Vogt S, Kelleher SL, (2010) X-ray fluorescence microscopy reveals accumulation and secretion of discrete intracellular zinc pools in the lactating mouse mammary gland. PLoS One 5: e11078.
39. Palmiter RD, (1994) Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1. Proc Natl Acad Sci U S A 91: 1219-1223.
40. Palmiter RD, Findley SD, (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14: 639-649.
41. Palmiter RD, Cole TB, Findley SD, (1996) ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO J 15: 1784-1791.
42. Lu M, Fu D, (2007) Structure of the zinc transporter YiiP. Science 317: 1746-1748.
43. Ohana E, Hoch E, Keisar C, Kambe T, Yifrach O, et al. (2009) Identification of the Zn2+ binding site and mode of operation of a mammalian Zn2+ transporter. J Biol Chem 284: 17677-17686.
44. Murgia C, Devirgiliis C, Mancini E, Donadel G, Zalewski P, et al. (2008) Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by distinct rodent endocrine cell types in the pancreas and other glands. Nutr Metab Cardiovasc Dis 19: 431-439.
45. Lu M, Chai J, Fu D, (2009) Structural basis for autoregulation of the zinc transporter YiiP. Nat Struct Mol Biol 16: 1063-1067.
46. Salazar G, Falcon-Perez JM, Harrison R, Faundez V, (2009) SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its subcellular localization and metal transport capacity. PLoS One 4: e5896.
47. Vazquez F, Ramaswamy S, Nakamura N, Sellers WR, (2000) Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol 20: 5010-5018.
48. Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T, (2006) Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5: 749-757.
49. Kambe T (2012). Molecular Architecture and Function of ZnT Transporters. In: Lutsenko S, Argüello JM, editors, Curr Top Membr. New York: Elsevier Inc.: Academic Press, 199-220.
50. Lin H, Burton D, Li L, Warner DE, Phillips JD, et al. (2009) Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity. Biochem J 422: 273-283.
51. Seo YA, Kelleher SL, (2010) Functional analysis of two single nucleotide polymorphisms in SLC30A2 (ZnT2): Implications for mammary gland function and breast disease in women. Physiol Genomics 42A: 219-227.
52. Qian L, Wang B, Tang N, Zhang W, Cai W, (2012) Polymorphisms of SLC30A2 and selected perinatal factors associated with low milk zinc in chinese breastfeeding women. Early Hum Dev 88: 663-668.
53. Lonnerdal B, (2007) Trace element transport in the mammary gland. Annu Rev Nutr 27: 165-177.
54. Kelleher SL, Seo YA, Lopez V, (2009) Mammary gland zinc metabolism: Regulation and dysregulation. Genes Nutr 4: 83-94.
55. Kelleher SL, McCormick NH, Velasquez V, Lopez V, (2011) Zinc in specialized secretory tissues: Roles in the pancreas, prostate, and mammary gland. Adv Nutr 2: 101-111.
56. Palmiter RD, Cole TB, Quaife CJ, Findley SD, (1996) ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci U S A 93: 14934-14939.
57. Zalewski PD, Millard SH, Forbes IJ, Kapaniris O, Slavotinek A, et al. (1994) Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc. J Histochem. Cytochem. 42: 877-884.
58. Sensi SL, Paoletti P, Bush AI, Sekler I, (2009) Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci 10: 780-791.
59. Kambe T, (2011) An overview of a wide range of functions of znt and zip zinc transporters in the secretory pathway. Biosci Biotechnol Biochem 75: 1036-1043.
60. Kambe T, Suzuki T, Nagao M, Yamaguchi-Iwai Y, (2006) Sequence similarity and functional relationship among eukaryotic ZIP and CDF transporters. Genomics Proteomics Bioinformatics 4: 1-9.
61. Cole TB, Wenzel HJ, Kafer KE, Schwartzkroin PA, Palmiter RD, (1999) Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci U S A 96: 1716-1721.
62. Lemaire K, Ravier MA, Schraenen A, Creemers JW, Van de Plas R, et al. (2009) Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci U S A 106: 14872-14877.
63. Adlard PA, Parncutt JM, Finkelstein D, Bush AI, (2010) Cognitive loss in zinc transporter-3 knock-out mice: A phenocopy for the synaptic and memory deficits of alzheimer's disease? J Neurosci 30: 1631-1636.
64. Rovelet-Lecrux A, Legallic S, Wallon D, Flaman JM, Martinaud O, et al. (2012) A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease Eur J Hum Genet. 20: 613-617.
65. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, et al. (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445: 881-885.
66. Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, et al. (2007) The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 104: 17040-17045.
67. Michalczyk AA, Allen J, Blomeley RC, Ackland ML, (2002) Constitutive expression of hZnT4 zinc transporter in human breast epithelial cells. Biochem J 364: 105-113.
68. McCormick NH, Kelleher SL, (2012) ZnT4 provides zinc to zinc-dependent proteins in the trans-golgi network critical for cell function and zn export in mammary epithelial cells. Am J Physiol Cell Physiol 303: C291-297.