亜鉛トランスポーターSlc39a13/Zip13：結合組織発生における役割とヒト遺伝性疾患への関与
『-亜鉛恒常性の制御とその意義について-』 亜鉛は, 亜鉛結合ドメインを介して多くの蛋白質の構造の維持や活性調節に貢献しており, 細胞の増殖, 分化, 移動, そして死が関わる生体応答の亜鉛による調節機構の存在が示唆される[1]. 最近のヒトゲノム配列の解読から, 約300以上の酵素が亜鉛を補酵素として要求し, さらに全遺伝子の約10%の蛋白質が亜鉛結合ドメインを有する可能性が示唆されており[2], これらのin silicoの情報だけを考えても亜鉛の必要性に疑う余地はない. 亜鉛は生体を構成する体液, 間質, 上皮および全ての細胞に存在し, ヒト成人(体重60kg)では総亜鉛量として約2gを...
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| Published in | BIOMEDICAL RESEARCH ON TRACE ELEMENTS Vol. 21; no. 1; pp. 17 - 24 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本微量元素学会
2010
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0916-717X 1880-1404 |
| DOI | 10.11299/brte.21.17 |
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| Abstract | 『-亜鉛恒常性の制御とその意義について-』 亜鉛は, 亜鉛結合ドメインを介して多くの蛋白質の構造の維持や活性調節に貢献しており, 細胞の増殖, 分化, 移動, そして死が関わる生体応答の亜鉛による調節機構の存在が示唆される[1]. 最近のヒトゲノム配列の解読から, 約300以上の酵素が亜鉛を補酵素として要求し, さらに全遺伝子の約10%の蛋白質が亜鉛結合ドメインを有する可能性が示唆されており[2], これらのin silicoの情報だけを考えても亜鉛の必要性に疑う余地はない. 亜鉛は生体を構成する体液, 間質, 上皮および全ての細胞に存在し, ヒト成人(体重60kg)では総亜鉛量として約2gを含有する. この総亜鉛量を維持する為には毎日約20mgの亜鉛摂取を必要とし, 食事から得られた亜鉛は亜鉛トランスポーターによって小腸粘膜を通過して吸収される. 成長過程における亜鉛の重要性は小児における亜鉛欠乏症によって広く認識されているが, そのきっかけはPrasadによる低身長と貧血を伴う小児疾患の発見であった[3]. |
|---|---|
| AbstractList | 『-亜鉛恒常性の制御とその意義について-』 亜鉛は, 亜鉛結合ドメインを介して多くの蛋白質の構造の維持や活性調節に貢献しており, 細胞の増殖, 分化, 移動, そして死が関わる生体応答の亜鉛による調節機構の存在が示唆される[1]. 最近のヒトゲノム配列の解読から, 約300以上の酵素が亜鉛を補酵素として要求し, さらに全遺伝子の約10%の蛋白質が亜鉛結合ドメインを有する可能性が示唆されており[2], これらのin silicoの情報だけを考えても亜鉛の必要性に疑う余地はない. 亜鉛は生体を構成する体液, 間質, 上皮および全ての細胞に存在し, ヒト成人(体重60kg)では総亜鉛量として約2gを含有する. この総亜鉛量を維持する為には毎日約20mgの亜鉛摂取を必要とし, 食事から得られた亜鉛は亜鉛トランスポーターによって小腸粘膜を通過して吸収される. 成長過程における亜鉛の重要性は小児における亜鉛欠乏症によって広く認識されているが, そのきっかけはPrasadによる低身長と貧血を伴う小児疾患の発見であった[3]. |
| Author | 深田, 俊幸 |
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| Copyright | 2010 日本微量元素学会 |
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| DOI | 10.11299/brte.21.17 |
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| References | 11) Dufner-Beattie J, Weaver BP, Geiser J, Bilgen M, Larson M, Xu W, et al. : The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency. Hum Mol Genet 16 : 1391-1399, 2007. 13) Kambe T, Weaver BP, Andrews GK : The genetics of essential metal homeostasis during development. Genesis 46 : 214-228, 2008. 15) Kagara N, Tanaka N, Noguchi S, Hirano T : Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells. Cancer Sci 98 : 692-697, 2007. 19) Cole TB, Robbins CA, Wenzel HJ, Schwartzkroin PA, Palmiter RD : Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res 39 : 153-169, 2000. 28) Lasswell J, Rogg LE, Nelson DC, Rongey C, Bartel B: Cloning and characterization of IAR1, a gene required for auxin conjugate sensitivity in Arabidopsis. Plant Cell 12 : 2395-2408, 2000. 14) Yamashita S, Miyagi C, Fukada T, Kagara N, Che YS, Hirano T : Zinc transporter LIVI controls epithelialmesenchymal transition in zebrafish gastrula organizer. Nature 429 : 298-302, 2004. 26) Chaudhuri A, Bowling K, Funderburk C, Lawal H, Inamdar A, Wang Z, et al. : Interaction of genetic and environmental factors in a Drosophila parkinsonism model. J Neurosci 27 : 2457-2467, 2007. 9) Peters JL, Dufner-Beattie J, Xu W, Geiser J, Lahner B, Salt DE, et al. Targeting of the mouse Slc39a2 (Zip2) gene reveals highly cell-specific patterns of expression, and unique functions in zinc, iron, and calcium homeostasis. Genesis 45 : 339-352, 2007. 2) Andreini C, Banci L, Bertini I, Rosato A. Counting the zinc-proteins encoded in the human genome. J Proteome Res 5 : 196-201, 2006. 30) Fukada T, Civic N, Furuichi T, Shimoda S, Mishima K, Higashiyama H, et al. : The zinc transporter SLC39 A13/ZIP13 is required for connective tissue development ; its involvement in BMP/TGF-beta signaling pathways. PLoS ONE 3 : e3642, 2008. 35) Miyazono K, Maeda S, Imamura T : BMP receptor signaling : transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16 : 251-263, 2005. 1) Hirano T, Murakami M, Fukada T, Nishida K, Yamasaki S, Suzuki T : Roles of zinc and zinc signaling in immunity : zinc as an intracellular signaling molecule. Adv Immunol 97 : 149-176, 2008. 12) Andrews GK, Wang H, Dey SK, Palmiter RD : Mouse zinc transporter 1 gene provides an essential function during early embryonic development. Genesis 40 : 74-81, 2004. 25) Stathakis DG, Burton DY, McIvor WE, Krishnakumar S, Wright TR, O'Donnell JM : The catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity. Genetics 153 : 361-382, 1999. 5) Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J: A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet 71 : 66-73, 2002. 24) Mathews WR, Ong D, Milutinovich AB, Van Doren M: Zinc transport activity of Fear of Intimacy is essential for proper gonad morphogenesis and DEcadherin expression. Development 133 : 1143-1153, 2006. 27) Hsouna A, Lawal HO, Izevbaye I, Hsu T, O'Donnell JM: Drosophila dopamine synthesis pathway genes regulate tracheal morphogenesis. Dev Biol 308 : 30-43, 2007. 17) Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. : Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 : 661-678, 2007. 10) Dufner-Beattie J, Huang ZL, Geiser J, Xu W, Andrews GK : Generation and characterization of mice lacking the zinc uptake transporter ZIP3. Mol Cell Biol 25 : 5607-5615, 2005. 16) Frayling TM : Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genetics 8 : 657-662, 2007. 21) Nishida K, Hasegawa A, Nakae S, Oboki K, Saito H, Yamasaki S, et al. : Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction. J Exp Med 206 : 1351-64, 2009. 31) Tucker A, Sharpe P : The cutting-edge of mammalian development ; how the embryo makes teeth. Nat Rev Genet 5 : 499-508, 2004. 23) Pielage J, Kippert A, Zhu M, Klambt C : The Drosophila transmembrane protein Fear-of-intimacy controls glial cell migration. Dev Biol 275 : 245-257, 2004. 7) Chowanadisai W, Lonnerdal B, Kelleher SL : 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, 2006. 6) Huang L, Gitschier J : A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17 : 292-297, 1997. 34) Giunta C, Elcioglu NH, Albrecht B, Eich G, Chambaz C, Janecke AR et al. : Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome - An autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet 82 : 1290-1305, 2008. 32) Rauch F, Glorieux FH : Osteogenesis imperfecta. Lancet 363 : 1377-1385, 2004. 36) 倉澤隆平．2005．高齢者と亜鉛．治療別冊87 : 9-15. 33) Mao JR, Bristow J : The Ehlers-Danlos syndrome : on beyond collagens. J Clin Invest 107 : 1063-1069, 2001. 4) Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, Kamoun R, et al. : Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31 : 239-240, 2002. 20) Inoue K, Matsuda K, Itoh M, KawaguchiH, Tomoike H, Aoyagi T, et al. : Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Hum Mol Genet 11 : 1775-1784, 2002. 3) Prasad AS, Halsted JA, Nadimi M : Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med 31 : 532-546, 1961. 8) Dufner-Beattie J, Huang ZXL, Geiser J, Xu WH, Andrews GK : Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy. Genesis 44 : 239-251, 2006. 18) Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin, JM, Gyulkhandanyan AV, et al. : Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58 : 2070-83, 2009. 22) Van Doren M, Mathews WR, Samuels M, Moore LA, Broihier HT, Lehmann R : Fear of intimacy encodes a novel transmembrane protein required for gonad morphogenesis in Drosophila. Development 130 : 2355-2364, 2003. 29) Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K: Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell 2 : 567-578, 2002. |
| References_xml | – reference: 7) Chowanadisai W, Lonnerdal B, Kelleher SL : 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, 2006. – reference: 2) Andreini C, Banci L, Bertini I, Rosato A. Counting the zinc-proteins encoded in the human genome. J Proteome Res 5 : 196-201, 2006. – reference: 11) Dufner-Beattie J, Weaver BP, Geiser J, Bilgen M, Larson M, Xu W, et al. : The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency. Hum Mol Genet 16 : 1391-1399, 2007. – reference: 16) Frayling TM : Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genetics 8 : 657-662, 2007. – reference: 25) Stathakis DG, Burton DY, McIvor WE, Krishnakumar S, Wright TR, O'Donnell JM : The catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity. Genetics 153 : 361-382, 1999. – reference: 27) Hsouna A, Lawal HO, Izevbaye I, Hsu T, O'Donnell JM: Drosophila dopamine synthesis pathway genes regulate tracheal morphogenesis. Dev Biol 308 : 30-43, 2007. – reference: 8) Dufner-Beattie J, Huang ZXL, Geiser J, Xu WH, Andrews GK : Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy. Genesis 44 : 239-251, 2006. – reference: 10) Dufner-Beattie J, Huang ZL, Geiser J, Xu W, Andrews GK : Generation and characterization of mice lacking the zinc uptake transporter ZIP3. Mol Cell Biol 25 : 5607-5615, 2005. – reference: 15) Kagara N, Tanaka N, Noguchi S, Hirano T : Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells. Cancer Sci 98 : 692-697, 2007. – reference: 36) 倉澤隆平．2005．高齢者と亜鉛．治療別冊87 : 9-15. – reference: 13) Kambe T, Weaver BP, Andrews GK : The genetics of essential metal homeostasis during development. Genesis 46 : 214-228, 2008. – reference: 19) Cole TB, Robbins CA, Wenzel HJ, Schwartzkroin PA, Palmiter RD : Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res 39 : 153-169, 2000. – reference: 17) Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. : Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 : 661-678, 2007. – reference: 3) Prasad AS, Halsted JA, Nadimi M : Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med 31 : 532-546, 1961. – reference: 35) Miyazono K, Maeda S, Imamura T : BMP receptor signaling : transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16 : 251-263, 2005. – reference: 32) Rauch F, Glorieux FH : Osteogenesis imperfecta. Lancet 363 : 1377-1385, 2004. – reference: 6) Huang L, Gitschier J : A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17 : 292-297, 1997. – reference: 22) Van Doren M, Mathews WR, Samuels M, Moore LA, Broihier HT, Lehmann R : Fear of intimacy encodes a novel transmembrane protein required for gonad morphogenesis in Drosophila. Development 130 : 2355-2364, 2003. – reference: 31) Tucker A, Sharpe P : The cutting-edge of mammalian development ; how the embryo makes teeth. Nat Rev Genet 5 : 499-508, 2004. – reference: 5) Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J: A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet 71 : 66-73, 2002. – reference: 24) Mathews WR, Ong D, Milutinovich AB, Van Doren M: Zinc transport activity of Fear of Intimacy is essential for proper gonad morphogenesis and DEcadherin expression. Development 133 : 1143-1153, 2006. – reference: 30) Fukada T, Civic N, Furuichi T, Shimoda S, Mishima K, Higashiyama H, et al. : The zinc transporter SLC39 A13/ZIP13 is required for connective tissue development ; its involvement in BMP/TGF-beta signaling pathways. PLoS ONE 3 : e3642, 2008. – reference: 14) Yamashita S, Miyagi C, Fukada T, Kagara N, Che YS, Hirano T : Zinc transporter LIVI controls epithelialmesenchymal transition in zebrafish gastrula organizer. Nature 429 : 298-302, 2004. – reference: 4) Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, Kamoun R, et al. : Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31 : 239-240, 2002. – reference: 12) Andrews GK, Wang H, Dey SK, Palmiter RD : Mouse zinc transporter 1 gene provides an essential function during early embryonic development. Genesis 40 : 74-81, 2004. – reference: 33) Mao JR, Bristow J : The Ehlers-Danlos syndrome : on beyond collagens. J Clin Invest 107 : 1063-1069, 2001. – reference: 20) Inoue K, Matsuda K, Itoh M, KawaguchiH, Tomoike H, Aoyagi T, et al. : Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Hum Mol Genet 11 : 1775-1784, 2002. – reference: 21) Nishida K, Hasegawa A, Nakae S, Oboki K, Saito H, Yamasaki S, et al. : Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction. J Exp Med 206 : 1351-64, 2009. – reference: 28) Lasswell J, Rogg LE, Nelson DC, Rongey C, Bartel B: Cloning and characterization of IAR1, a gene required for auxin conjugate sensitivity in Arabidopsis. Plant Cell 12 : 2395-2408, 2000. – reference: 34) Giunta C, Elcioglu NH, Albrecht B, Eich G, Chambaz C, Janecke AR et al. : Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome - An autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet 82 : 1290-1305, 2008. – reference: 1) Hirano T, Murakami M, Fukada T, Nishida K, Yamasaki S, Suzuki T : Roles of zinc and zinc signaling in immunity : zinc as an intracellular signaling molecule. Adv Immunol 97 : 149-176, 2008. – reference: 9) Peters JL, Dufner-Beattie J, Xu W, Geiser J, Lahner B, Salt DE, et al. Targeting of the mouse Slc39a2 (Zip2) gene reveals highly cell-specific patterns of expression, and unique functions in zinc, iron, and calcium homeostasis. Genesis 45 : 339-352, 2007. – reference: 23) Pielage J, Kippert A, Zhu M, Klambt C : The Drosophila transmembrane protein Fear-of-intimacy controls glial cell migration. Dev Biol 275 : 245-257, 2004. – reference: 18) Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin, JM, Gyulkhandanyan AV, et al. : Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58 : 2070-83, 2009. – reference: 29) Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K: Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell 2 : 567-578, 2002. – reference: 26) Chaudhuri A, Bowling K, Funderburk C, Lawal H, Inamdar A, Wang Z, et al. : Interaction of genetic and environmental factors in a Drosophila parkinsonism model. J Neurosci 27 : 2457-2467, 2007. |
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| SubjectTerms | BMP connective tissue Ehlers-Danlos syndrome Slc39a13/Zip13 TGF-β Zinc transporter |
| Title | 亜鉛トランスポーターSlc39a13/Zip13：結合組織発生における役割とヒト遺伝性疾患への関与 |
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| ispartofPNX | Biomedical Research on Trace Elements, 2010, Vol.21(1), pp.17-24 |
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