Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Weinheim : WILEY-VCH, [2014]-
    • Subject Terms:
      Zinc*/metabolism ; Homeostasis*/genetics ; Homeostasis*/physiology ; Cation Transport Proteins*/metabolism ; Cation Transport Proteins*/genetics ; Mice, Knockout*; Animals ; Mice ; Humans ; Intestinal Mucosa/metabolism
    • Abstract:
      The essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal-responsive transcriptional regulators are linked to zinc homeostasis. However, the mechanism underlying the regulation of systemic zinc homeostasis remains largely unknown. Here, it is reported that the intestinal transporter SLC30A1 plays an essential role in maintaining systemic zinc homeostasis. Using several lines of tissue-specific knockout mice, it is found that intestinal Slc30a1 plays a critical role in survival. Furthermore, lineage tracing reveals that Slc30a1 is localized to the basolateral membrane of intestinal epithelial cells (IECs). It is also found that Slc30a1 safeguards both intestinal barrier integrity and systemic zinc homeostasis. Finally, an integrative analysis of the cryo-EM structure and site-specific mutagenesis of human SLC30A1 are performed and a zinc transport mechanism of SLC30A1 unique within the SLC30A family, with His43 serving as a critical residue for zinc selectivity, is identified.
      (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
    • References:
      Annu Rev Nutr. 2004;24:151-72. (PMID: 15189117)
      J Struct Biol. 2016 Jan;193(1):1-12. (PMID: 26592709)
      PLoS One. 2012;7(10):e48679. (PMID: 23110240)
      Cell. 2014 Jan 16;156(1-2):317-331. (PMID: 24439385)
      Gastroenterology. 2012 Jun;142(7):1536-46.e5. (PMID: 22374166)
      Hum Mol Genet. 2004 Mar 1;13(5):563-71. (PMID: 14709598)
      J Res Med Sci. 2013 Feb;18(2):144-57. (PMID: 23914218)
      Biochem J. 2009 Jul 29;422(1):43-52. (PMID: 19496757)
      Nat Chem Biol. 2017 Jan;13(1):91-98. (PMID: 27842070)
      Methods Enzymol. 2016;579:125-57. (PMID: 27572726)
      Nat Genet. 2002 Jul;31(3):239-40. (PMID: 12068297)
      EMBO J. 1995 Feb 15;14(4):639-49. (PMID: 7882967)
      J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254)
      Elife. 2020 Feb 04;9:. (PMID: 32014109)
      Aliment Pharmacol Ther. 2023 Feb;57(4):399-408. (PMID: 36645152)
      J Biol Chem. 2019 Oct 25;294(43):15686-15697. (PMID: 31471319)
      Nat Rev Mol Cell Biol. 2021 Jan;22(1):39-53. (PMID: 32958874)
      Mol Cell Biol. 2005 Jul;25(13):5607-15. (PMID: 15964816)
      J Biol Chem. 2016 Jul 8;291(28):14773-87. (PMID: 27226609)
      Nat Commun. 2018 Jul 20;9(1):2872. (PMID: 30030441)
      Adv Nutr. 2016 Jul 15;7(4):735-46. (PMID: 27422508)
      Inflamm Bowel Dis. 2017 Jan;23(1):152-157. (PMID: 27930412)
      Int J Epidemiol. 2015 Dec;44(6):1995-2005. (PMID: 26546032)
      Nat Methods. 2019 Jun;16(6):471-477. (PMID: 31086343)
      Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12940-12945. (PMID: 29180421)
      Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844)
      Diabetes. 2009 Sep;58(9):2070-83. (PMID: 19542200)
      Biochem J. 2009 Jul 15;421(3):371-6. (PMID: 19450229)
      Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444. (PMID: 34791371)
      J Biol Chem. 2003 Aug 29;278(35):33474-81. (PMID: 12801924)
      Behav Brain Res. 2011 Sep 30;223(1):233-8. (PMID: 21545813)
      Chem Rev. 2021 Dec 8;121(23):14594-14648. (PMID: 34652893)
      Diabetologia. 2008 Apr;51(4):597-601. (PMID: 18264689)
      Nat Genet. 2023 Oct;55(10):1623-1631. (PMID: 37709865)
      Genesis. 2007 Jun;45(6):339-52. (PMID: 17506078)
      Int J Mol Sci. 2022 Mar 26;23(7):. (PMID: 35408994)
      Adv Sci (Weinh). 2024 Dec;11(46):e2406421. (PMID: 39422023)
      J Chem Inf Model. 2016 Dec 27;56(12):2287-2291. (PMID: 27976886)
      N Engl J Med. 2014 Jan 30;370(5):455-65. (PMID: 24476434)
      Cell Rep. 2023 Jun 27;42(6):112656. (PMID: 37330912)
      Genesis. 2004 Oct;40(2):74-81. (PMID: 15452870)
      PLoS Genet. 2017 Jul 10;13(7):e1006892. (PMID: 28692648)
      Adv Nutr. 2013 Mar 01;4(2):176-90. (PMID: 23493534)
      Nutrients. 2023 Apr 20;15(8):. (PMID: 37111210)
      Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32. (PMID: 15572765)
      Science. 2013 Feb 15;339(6121):786-91. (PMID: 23258413)
      J Nutr. 2001 Jan;131(1):46-52. (PMID: 11208937)
      Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702)
      Science. 2013 Feb 15;339(6121):826-30. (PMID: 23258412)
      Physiol Rev. 2015 Jul;95(3):749-84. (PMID: 26084690)
      Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303. (PMID: 29788355)
      PLoS One. 2008;3(11):e3642. (PMID: 18985159)
      Cell. 2012 Jan 20;148(1-2):213-27. (PMID: 22265413)
      Protein Cell. 2019 Jun;10(6):436-449. (PMID: 30324491)
      Clin Nutr. 2021 Jan;40(1):327-331. (PMID: 32517876)
      Annu Rev Nutr. 2009;29:153-76. (PMID: 19400752)
      J Nutr. 2000 May;130(5S Suppl):1360S-6S. (PMID: 10801944)
      J Biol Chem. 2007 May 11;282(19):14389-93. (PMID: 17355957)
      Sci Signal. 2012 Mar 06;5(214):ra20. (PMID: 22394562)
      J Histochem Cytochem. 2007 Mar;55(3):223-34. (PMID: 17101726)
      J Biol Chem. 2007 Dec 21;282(51):37053-63. (PMID: 17954933)
      Cell Metab. 2005 Mar;1(3):191-200. (PMID: 16054062)
      Clin Exp Med. 2024 Feb 17;24(1):38. (PMID: 38367035)
      Nat Methods. 2017 Apr;14(4):331-332. (PMID: 28250466)
      Elife. 2020 Jul 29;9:. (PMID: 32723473)
      Nature. 2019 May;569(7754):66-72. (PMID: 31019299)
      Adv Sci (Weinh). 2023 Jun;10(17):e2205345. (PMID: 37068188)
      Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1716-21. (PMID: 9990090)
      Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680. (PMID: 30692261)
      Cell. 2021 Jan 7;184(1):149-168.e17. (PMID: 33278357)
      Nature. 2023 Aug;620(7973):374-380. (PMID: 37532932)
      Hum Mol Genet. 2007 Jun 15;16(12):1391-9. (PMID: 17483098)
      Nat Rev Mol Cell Biol. 2008 May;9(5):378-90. (PMID: 18414491)
      Hepatology. 2024 Aug 1;80(2):312-329. (PMID: 37816045)
      Protein Sci. 2018 Jan;27(1):14-25. (PMID: 28710774)
      Genesis. 2006 May;44(5):239-51. (PMID: 16652366)
      Am J Hum Genet. 2002 Jul;71(1):66-73. (PMID: 12032886)
      Inflamm Bowel Dis. 2012 Feb;18(2):E399. (PMID: 21994075)
    • Grant Information:
      31930057 National Natural Science Foundation of China; 32330047 National Natural Science Foundation of China; 82471593 National Natural Science Foundation of China; 32100941 National Natural Science Foundation of China; 32100940 National Natural Science Foundation of China
    • Contributed Indexing:
      Keywords: SLC30A1 structure; intestinal barrier integrity; ion selectivity; zinc homeostasis
    • Accession Number:
      J41CSQ7QDS (Zinc)
      0 (Cation Transport Proteins)
      0 (SLC30A1 protein, human)
      0 (Slc30a1 protein, mouse)
    • Publication Date:
      Date Created: 20241018 Date Completed: 20241211 Latest Revision: 20241213
    • Publication Date:
      20241213
    • Accession Number:
      PMC11633486
    • Accession Number:
      10.1002/advs.202406421
    • Accession Number:
      39422023