The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Pearse BR;Pearse BR; Tamura T; Sunryd JC; Grabowski GA; Kaufman RJ; Hebert DN
  • Source:
    The Journal of cell biology [J Cell Biol] 2010 May 31; Vol. 189 (5), pp. 829-41. Date of Electronic Publication: 2010 May 24.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 0375356 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-8140 (Electronic) Linking ISSN: 00219525 NLM ISO Abbreviation: J Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York : Rockefeller University Press
    • Subject Terms:
      Protein Folding*; Glucosyltransferases/*metabolism ; Protein Processing, Post-Translational/*physiology ; Saposins/*metabolism; Animals ; CHO Cells ; Calnexin/metabolism ; Calreticulin/metabolism ; Catalytic Domain/genetics ; Cricetinae ; Cricetulus ; Detergents/chemistry ; Endoplasmic Reticulum/metabolism ; Fibroblasts/metabolism ; Glucosyltransferases/genetics ; Golgi Apparatus/metabolism ; Humans ; Inclusion Bodies/metabolism ; Mice ; Mutation/physiology ; Protein Conformation ; Saposins/chemistry ; Saposins/genetics ; Solubility ; Vimentin/metabolism
    • Abstract:
      An endoplasmic reticulum (ER) quality control system assists in efficient folding and disposal of misfolded proteins. N-linked glycans are critical in these events because their composition dictates interactions with molecular chaperones. UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1) is a key quality control factor of the ER. It adds glucoses to N-linked glycans of nonglucosylated substrates that fail a quality control test, supporting additional rounds of chaperone binding and ER retention. How UGT1 functions in its native environment is poorly understood. The role of UGT1 in the maturation of glycoproteins at basal expression levels was analyzed. Prosaposin was identified as a prominent endogenous UGT1 substrate. A dramatic decrease in the secretion of prosaposin was observed in ugt1(-/-) cells with prosaposin localized to large juxtanuclear aggresome-like inclusions, which is indicative of its misfolding and the essential role that UGT1 plays in its proper maturation. A model is proposed that explains how UGT1 may aid in the folding of sequential domain-containing proteins such as prosaposin.
    • References:
      J Biol Chem. 1984 May 25;259(10):6351-7. (PMID: 6373756)
      Arch Biochem Biophys. 1993 Jun;303(2):326-31. (PMID: 8099782)
      Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6229-33. (PMID: 7541532)
      Cell. 2009 Jan 23;136(2):272-83. (PMID: 19167329)
      EMBO J. 2008 Aug 6;27(15):2043-54. (PMID: 18650939)
      J Lipid Res. 1992 Sep;33(9):1255-67. (PMID: 1402395)
      J Cell Biol. 1998 Dec 28;143(7):1883-98. (PMID: 9864362)
      Physiol Rev. 2007 Oct;87(4):1377-408. (PMID: 17928587)
      Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):913-7. (PMID: 8302866)
      Structure. 2008 May;16(5):809-17. (PMID: 18462685)
      Mol Biol Cell. 1994 Mar;5(3):253-65. (PMID: 8049518)
      EMBO J. 1998 Oct 15;17(20):5877-86. (PMID: 9774332)
      EMBO J. 1996 Apr 1;15(7):1495-506. (PMID: 8612572)
      Biochemistry. 1986 Nov 18;25(23):7265-70. (PMID: 3801415)
      Hum Mol Genet. 2007 Apr 15;16(8):957-71. (PMID: 17353235)
      J Androl. 2000 Nov-Dec;21(6):765-75. (PMID: 11105903)
      Mol Biol Cell. 1995 Sep;6(9):1173-84. (PMID: 8534914)
      J Biol Chem. 2003 Oct 31;278(44):43320-8. (PMID: 12913004)
      J Cell Biol. 2008 Apr 21;181(2):309-20. (PMID: 18426978)
      Trends Biochem Sci. 2004 Oct;29(10):527-34. (PMID: 15450607)
      EMBO J. 2003 Dec 15;22(24):6430-7. (PMID: 14657016)
      Annu Rev Biochem. 2005;74:739-89. (PMID: 15952902)
      J Biol Chem. 2005 May 6;280(18):18138-41. (PMID: 15746090)
      Biochemistry. 1989 Oct 3;28(20):8108-16. (PMID: 2532539)
      Cell. 2003 Dec 12;115(6):727-38. (PMID: 14675537)
      Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):86-91. (PMID: 12518055)
      Science. 1994 Jan 21;263(5145):387-90. (PMID: 8278814)
      Hum Mol Genet. 2008 Aug 1;17(15):2345-56. (PMID: 18480170)
      J Biol Chem. 2004 Oct 29;279(44):46280-5. (PMID: 15319428)
      Biochem J. 2004 Nov 1;383(Pt. 3):507-15. (PMID: 15255780)
      J Biol Chem. 2000 Apr 28;275(17):13089-97. (PMID: 10777614)
      Mol Cell. 2007 Jul 20;27(2):238-49. (PMID: 17643373)
      EMBO J. 1996 Jun 17;15(12):2961-8. (PMID: 8670797)
      EMBO J. 1995 Sep 1;14(17):4196-203. (PMID: 7556060)
      Glycobiology. 1998 Jul;8(7):725-30. (PMID: 9621113)
      J Cell Biol. 1991 Nov;115(4):983-94. (PMID: 1955467)
      Cell Motil Cytoskeleton. 2002 Sep;53(1):26-38. (PMID: 12211113)
      Mol Biol Cell. 1999 May;10(5):1381-94. (PMID: 10233151)
      J Biol Chem. 2003 Jun 6;278(23):20540-6. (PMID: 12649273)
      Mol Cell. 2005 Nov 23;20(4):503-12. (PMID: 16307915)
      PLoS Biol. 2006 Nov;4(11):e374. (PMID: 17090218)
      Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9593-6. (PMID: 7937812)
      EMBO J. 1997 Sep 1;16(17):5420-32. (PMID: 9312001)
      J Biol Chem. 2008 Dec 5;283(49):33826-37. (PMID: 18849342)
      J Biol Chem. 1995 Sep 1;270(35):20298-304. (PMID: 7657600)
      Mol Biol Cell. 2001 Jun;12(6):1711-23. (PMID: 11408579)
      Annu Rev Biochem. 2004;73:1019-49. (PMID: 15189166)
      Biochem Biophys Res Commun. 1991 Nov 27;181(1):286-92. (PMID: 1958198)
      J Biol Chem. 1991 Nov 15;266(32):21458-65. (PMID: 1939178)
      J Biol Chem. 1998 Mar 13;273(11):6009-12. (PMID: 9497314)
      EMBO Rep. 2003 Apr;4(4):405-11. (PMID: 12671684)
      Nat Struct Mol Biol. 2004 Feb;11(2):128-34. (PMID: 14730348)
      Science. 1997 Jan 3;275(5296):86-8. (PMID: 8974399)
      Glycobiology. 1999 Jan;9(1):65-72. (PMID: 9884408)
      J Biol Chem. 2008 Apr 18;283(16):10221-5. (PMID: 18303019)
      Mol Cell. 2003 Jan;11(1):79-90. (PMID: 12535523)
      Cell. 1995 May 5;81(3):425-33. (PMID: 7736594)
      J Cell Biol. 1997 Nov 3;139(3):613-23. (PMID: 9348279)
      Biochim Biophys Acta. 1999 Dec 6;1473(1):4-8. (PMID: 10580125)
      Glycobiology. 2000 Apr;10(4):403-12. (PMID: 10764828)
      J Biol Chem. 1995 Apr 28;270(17):9953-60. (PMID: 7730378)
      J Biol Chem. 2006 Mar 10;281(10):6219-26. (PMID: 16407314)
      J Biol Chem. 2003 Feb 21;278(8):6194-200. (PMID: 12464625)
      J Biol Chem. 1997 Feb 14;272(7):4179-86. (PMID: 9020131)
      FASEB J. 2001 Feb;15(2):467-74. (PMID: 11156962)
      Biochemistry. 1992 Jan 14;31(1):97-105. (PMID: 1531024)
      Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4778-81. (PMID: 9114068)
      Nat Rev Mol Cell Biol. 2003 Mar;4(3):181-91. (PMID: 12612637)
      Biochemistry. 1988 Jun 14;27(12):4557-64. (PMID: 3048385)
    • Grant Information:
      R01 DK088227 United States DK NIDDK NIH HHS; GM086874 United States GM NIGMS NIH HHS; R37 DK042394 United States DK NIDDK NIH HHS; T32GM00815 United States GM NIGMS NIH HHS; R01 CA079864 United States CA NCI NIH HHS; DK42394 United States DK NIDDK NIH HHS; CA79864 United States CA NCI NIH HHS; NS36681 United States NS NINDS NIH HHS; R01 NS036681 United States NS NINDS NIH HHS; P01 HL057346 United States HL NHLBI NIH HHS; T32 GM008515 United States GM NIGMS NIH HHS; R01 DK036729 United States DK NIDDK NIH HHS; R01 GM086874 United States GM NIGMS NIH HHS; United States HHMI Howard Hughes Medical Institute; HL52173 United States HL NHLBI NIH HHS; R01 DK042394 United States DK NIDDK NIH HHS; R01 HL052173 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Calreticulin)
      0 (Detergents)
      0 (Psap protein, mouse)
      0 (Saposins)
      0 (Vimentin)
      139873-08-8 (Calnexin)
      EC 2.4.1.- (Glucosyltransferases)
      EC 2.4.1.- (mannosylglycoprotein 1,3-glucosyltransferase)
    • Publication Date:
      Date Created: 20100526 Date Completed: 20100719 Latest Revision: 20240922
    • Publication Date:
      20250114
    • Accession Number:
      PMC2878942
    • Accession Number:
      10.1083/jcb.200912105
    • Accession Number:
      20498017