In vivo expression of peptidylarginine deiminase in Drosophila melanogaster.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
    • Abstract:
      Peptidylarginine deiminase (PAD) modifies peptidylarginine and converts it to peptidylcitrulline in the presence of elevated calcium. Protein modification can lead to severe changes in protein structure and function, and aberrant PAD activity is linked to human pathologies. While PAD homologs have been discovered in vertebrates-as well as in protozoa, fungi, and bacteria-none have been identified in Drosophila melanogaster, a simple and widely used animal model for human diseases. Here, we describe the development of a human PAD overexpression model in Drosophila. We established fly lines harboring human PAD2 or PAD4 transgenes for ectopic expression under control of the GAL4/UAS system. We show that ubiquitous or nervous system expression of PAD2 or PAD4 have minimal impact on fly lifespan, fecundity, and the response to acute heat stress. Although we did not detect citrullinated proteins in fly homogenates, fly-expressed PAD4-but not PAD2-was active in vitro upon Ca2+ supplementation. The transgenic fly lines may be valuable in future efforts to develop animal models of PAD-related disorders and for investigating the biochemistry and regulation of PAD function.
      Competing Interests: The authors have declared that no competing interests exist.
    • References:
      J Clin Invest. 1994 Jul;94(1):146-54. (PMID: 7518827)
      Dev Comp Immunol. 2018 Oct;87:157-170. (PMID: 29908202)
      J Biochem. 1981 Jan;89(1):257-63. (PMID: 7217033)
      Nature. 2014 Mar 6;507(7490):104-8. (PMID: 24463520)
      BMC Dev Biol. 2012 Jun 19;12:19. (PMID: 22712504)
      Comp Biochem Physiol B Biochem Mol Biol. 2014 Jan;167:65-73. (PMID: 24161753)
      Protein Sci. 2019 Mar;28(3):478-486. (PMID: 30638292)
      Biochem Biophys Res Commun. 1996 Aug 23;225(3):712-9. (PMID: 8780679)
      Mol Neurobiol. 2018 Apr;55(4):3172-3184. (PMID: 28470584)
      Mol Neurobiol. 2019 Apr;56(4):2618-2639. (PMID: 30051351)
      Sci Transl Med. 2013 May 22;5(186):186ra65. (PMID: 23698378)
      Development. 1993 Jun;118(2):401-15. (PMID: 8223268)
      ACS Chem Biol. 2015 Apr 17;10(4):1043-53. (PMID: 25621824)
      PLoS One. 2012;7(7):e41242. (PMID: 22911765)
      J Neurosci. 2006 Nov 1;26(44):11387-96. (PMID: 17079667)
      Eur J Dermatol. 2011 May-Jun;21(3):376-84. (PMID: 21697043)
      Mol Cell Neurosci. 2004 Jul;26(3):365-75. (PMID: 15234342)
      Enzyme Microb Technol. 2019 May;124:41-53. (PMID: 30797478)
      Cancer Res. 2014 Nov 1;74(21):6306-17. (PMID: 25213324)
      J Cell Sci. 2008 Sep 1;121(Pt 17):2930-8. (PMID: 18697833)
      Biochemistry. 2005 Aug 9;44(31):10570-82. (PMID: 16060666)
      Dev Comp Immunol. 2019 Mar;92:1-19. (PMID: 30395876)
      J Biol Chem. 2014 Nov 21;289(47):32481-7. (PMID: 25324545)
      Aging Cell. 2008 Jun;7(3):441-4. (PMID: 18248664)
      J Neurosci. 2006 Nov 29;26(48):12408-14. (PMID: 17135402)
      PLoS One. 2011;6(6):e21314. (PMID: 21731701)
      J Dermatol Sci. 2006 Nov;44(2):63-72. (PMID: 16973334)
      Science. 1982 Oct 22;218(4570):348-53. (PMID: 6289436)
      Sci Transl Med. 2013 Mar 27;5(178):178ra40. (PMID: 23536012)
      J Autoimmun. 2012 Jun;38(4):369-80. (PMID: 22560840)
      J Neurosci Res. 2005 Apr 1;80(1):120-8. (PMID: 15704193)
      Gene. 2004 Apr 14;330:19-27. (PMID: 15087120)
      J Neurochem. 2003 Jun;85(6):1614-23. (PMID: 12787080)
      Biochim Biophys Acta. 2014 Sep;1843(9):1805-17. (PMID: 24751693)
      Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6623-8. (PMID: 15069204)
      Prion. 2013 Jan-Feb;7(1):42-6. (PMID: 23022892)
      Acta Neuropathol. 2010 Feb;119(2):199-210. (PMID: 20013286)
      Dis Model Mech. 2008 Nov-Dec;1(4-5):229-40. (PMID: 19093029)
      J Neurophysiol. 2008 May;99(5):2420-30. (PMID: 18272873)
      Front Cell Infect Microbiol. 2019 Jun 27;9:227. (PMID: 31316918)
      Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18633-7. (PMID: 19841272)
      J Biol Chem. 2011 May 13;286(19):17069-78. (PMID: 21454715)
      Curr Opin Drug Discov Devel. 2009 Sep;12(5):616-27. (PMID: 19736621)
      Science. 2004 Oct 8;306(5694):279-83. (PMID: 15345777)
      Nat Struct Mol Biol. 2004 Aug;11(8):777-83. (PMID: 15247907)
      Cell Tissue Res. 2017 Nov;370(2):275-283. (PMID: 28766045)
      J Extracell Vesicles. 2015 Jun 19;4:26192. (PMID: 26095379)
      J Neurochem. 1993 Sep;61(3):987-96. (PMID: 7689646)
      Mol Biol Rep. 2010 Jun;37(5):2333-9. (PMID: 19693695)
      J Neurophysiol. 2002 Nov;88(5):2659-63. (PMID: 12424301)
      Biochemistry. 2006 Oct 3;45(39):11727-36. (PMID: 17002273)
      Int J Biochem Cell Biol. 2006;38(10):1662-77. (PMID: 16730216)
      Fish Shellfish Immunol. 2019 Sep;92:249-255. (PMID: 31200072)
    • Grant Information:
      R01 AG045036 United States AG NIA NIH HHS; R56 AG065986 United States AG NIA NIH HHS
    • Accession Number:
      EC 3.5.3.15 (PADI2 protein, human)
      EC 3.5.3.15 (PADI4 protein, human)
      EC 3.5.3.15 (Protein-Arginine Deiminase Type 2)
      EC 3.5.3.15 (Protein-Arginine Deiminase Type 4)
    • Publication Date:
      Date Created: 20200116 Date Completed: 20200416 Latest Revision: 20201213
    • Publication Date:
      20240105
    • Accession Number:
      PMC6961906
    • Accession Number:
      10.1371/journal.pone.0227822
    • Accession Number:
      31940417