The effects of WWP1 overexpression on the golgi apparatus stress response and proteoglycan production in adipocytes.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Golgi Apparatus*/metabolism ; Ubiquitin-Protein Ligases*/metabolism ; Ubiquitin-Protein Ligases*/genetics ; Proteoglycans*/metabolism ; Proteoglycans*/genetics ; 3T3-L1 Cells* ; Adipocytes*/metabolism; Animals ; Mice ; Obesity/metabolism ; Obesity/genetics ; Mice, Knockout ; Glycosylation
    • Abstract:
      White adipocytes are a major component of white adipose tissue (WAT) and help to maintain systemic metabolic homeostasis by storing energy and secreting adipokines. In mice deficient in the protein WWP1 (WW domain-containing E3 ubiquitin protein ligase 1), oxidative stress in adipocytes increases but insulin resistance induced by obesity improves. However, the specific roles of WWP1 in adipocytes remain unclear. Here, we show that in 3T3L1 adipocytes, WWP1 localized in the Golgi apparatus via its C2 domain, where it protected the Golgi apparatus from monensin-induced disruption. By contrast, WWP1 knockdown by short hairpin RNA failed to protect the Golgi apparatus and enhanced Golgi apparatus disruption by monensin. The Golgi apparatus acts as a central organelle to establish accurate protein glycosylation of proteoglycans containing glycosaminoglycans, including chondroitin sulfate and heparan sulfate (HS). WWP1 overexpression increased chondroitin sulfate and HS levels, whereas WWP1 knockdown decreased them. Furthermore, obesity-related increases in HS were prevented by WWP1 knockout in adipose tissue. In summary, our results demonstrate a novel role for WWP1 in maintaining Golgi apparatus morphology and proteoglycan synthesis in adipocytes.
      Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
      (© 2024. The Author(s).)
    • References:
      Aging Cell. 2017 Jun;16(3):508-517. (PMID: 28256090)
      J Mol Endocrinol. 2007 Jul;39(1):45-52. (PMID: 17601884)
      Front Genet. 2014 Jul 25;5:242. (PMID: 25120559)
      Cell Death Discov. 2022 Mar 9;8(1):107. (PMID: 35264565)
      Biochem Biophys Res Commun. 2019 Jan 1;508(1):117-122. (PMID: 30471861)
      J Cell Biol. 1998 Mar 9;140(5):1013-21. (PMID: 9490716)
      Int J Obes (Lond). 2019 Sep;43(9):1783-1794. (PMID: 30778123)
      Curr Biol. 1995 Jun 1;5(6):635-42. (PMID: 7552174)
      Curr Opin Struct Biol. 2003 Oct;13(5):612-20. (PMID: 14568617)
      FEBS Open Bio. 2020 Mar;10(3):306-315. (PMID: 31965758)
      J Biol Chem. 1951 Nov;193(1):265-75. (PMID: 14907713)
      Cell Death Discov. 2021 Jun 21;7(1):163. (PMID: 34226507)
      J Biol Chem. 2020 Dec 25;295(52):18614-18624. (PMID: 33127645)
      Nature. 2006 Dec 14;444(7121):860-7. (PMID: 17167474)
      J Biol Chem. 2001 Nov 30;276(48):45298-306. (PMID: 11590181)
      Science. 2019 May 17;364(6441):. (PMID: 31097636)
      Cell Struct Funct. 2011;36(1):1-12. (PMID: 21150128)
      Biochem Biophys Res Commun. 2012 Nov 2;427(4):758-63. (PMID: 23041188)
      Biochim Biophys Acta. 1990 May 7;1031(2):225-46. (PMID: 2160275)
      Cell Biol Int Rep. 1992 Mar;16(3):217-20. (PMID: 1581967)
      J Mol Biol. 2016 Aug 14;428(16):3183-3193. (PMID: 26956395)
      Lipids Health Dis. 2005 Jan 06;4:2. (PMID: 15636641)
      J Virol. 1998 Oct;72(10):8150-7. (PMID: 9733856)
      Life Sci Alliance. 2021 Aug 17;4(10):. (PMID: 34404733)
      Mech Ageing Dev. 2012 May;133(5):255-66. (PMID: 22414572)
      J Biochem. 2016 Feb;159(2):171-9. (PMID: 26314333)
      Free Radic Biol Med. 2011 Apr 15;50(8):907-17. (PMID: 21241794)
      Sci Rep. 2019 Feb 4;9(1):1200. (PMID: 30718715)
      J Biol Chem. 2002 Mar 15;277(11):9307-17. (PMID: 11748237)
      Dev Cell. 2016 Jul 11;38(1):73-85. (PMID: 27404360)
      Nat Rev Immunol. 2011 Feb;11(2):85-97. (PMID: 21252989)
      EMBO J. 2004 Oct 1;23(19):3780-92. (PMID: 15359284)
      Cold Spring Harb Perspect Biol. 2011 Apr 01;3(4):. (PMID: 21441588)
      Nat Commun. 2020 Jan 21;11(1):409. (PMID: 31964869)
      Cell Struct Funct. 2015;40(1):13-30. (PMID: 25399611)
      J Cell Biol. 1998 Oct 19;143(2):319-31. (PMID: 9786945)
      Nat Commun. 2011 Oct 11;2:501. (PMID: 21988917)
      Sci Rep. 2021 Dec 6;11(1):23489. (PMID: 34873243)
      Nat Commun. 2013;4:1659. (PMID: 23552074)
      Cell Mol Life Sci. 2012 May;69(9):1425-34. (PMID: 22051607)
      FEBS Open Bio. 2023 Jun;13(6):1086-1094. (PMID: 37032433)
      Oncogene. 2007 Mar 1;26(10):1477-83. (PMID: 16924229)
      Carbohydr Polym. 2023 Aug 1;313:120847. (PMID: 37182947)
      J Clin Invest. 2004 Dec;114(12):1752-61. (PMID: 15599400)
      Annu Rev Biochem. 2014;83:129-57. (PMID: 24606135)
      Histochem Cell Biol. 1998 May-Jun;109(5-6):571-90. (PMID: 9681636)
    • Grant Information:
      23659207 Japan Society for the Promotion of Science
    • Contributed Indexing:
      Keywords: Adipose tissue; Glycosaminoglycan; Golgi apparatus; WWP1
    • Accession Number:
      EC 2.3.2.27 (Ubiquitin-Protein Ligases)
      0 (Proteoglycans)
      EC 2.3.2.26 (WWP1 protein, mouse)
    • Publication Date:
      Date Created: 20241123 Date Completed: 20241123 Latest Revision: 20241126
    • Publication Date:
      20241202
    • Accession Number:
      PMC11584891
    • Accession Number:
      10.1038/s41598-024-79114-7
    • Accession Number:
      39578509