title: Golgi phosphoprotein 3 mediates the Golgi localization and function of protein O-linked mannose β-1,2-N-acetlyglucosaminyltransferase 1.
abstract: GOLPH3 is a highly conserved protein found across the eukaryotic lineage. The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of α-dystroglycan. The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of α-dystroglycan. In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, highlighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. Our findings reveal a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1.
authors.affiliation: From the Bioprocessing Technology Institute, Agency for Science, Technology, and Research (A*STAR), 20 Biopolis Way, 06-01 Centros, 138668, Singapore.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Pereira
authors.affiliation: From the Bioprocessing Technology Institute, Agency for Science, Technology, and Research (A*STAR), 20 Biopolis Way, 06-01 Centros, 138668, Singapore.
authors.forename: Helen X
authors.initials: HX
authors.lastname: Pu
authors.affiliation: From the Bioprocessing Technology Institute, Agency for Science, Technology, and Research (A*STAR), 20 Biopolis Way, 06-01 Centros, 138668, Singapore.
authors.forename: Hazel
authors.initials: H
authors.lastname: Goh
authors.affiliation: From the Bioprocessing Technology Institute, Agency for Science, Technology, and Research (A*STAR), 20 Biopolis Way, 06-01 Centros, 138668, Singapore song_zhiwei@bti.a-star.edu.sg.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Song
mesh_terms: D015153:Blotting, Western; D049030:Dystroglycans / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase
keywords: GOLPH3; Glycosylation; Glycosyltransferases; Muscle-eye Brain Disease; POMGnT; Protein Targeting; Protein-protein Interactions; Skeletal Muscle
references.citation: J Cell Sci. 2006 Jan 15;119(Pt 2):199-207
references.pmid: 16410545
references.citation: Biochem Biophys Res Commun. 1999 Feb 16;255(2):194-9
references.pmid: 10049685
references.citation: Nature. 1991 Aug 15;352(6336):624-8
references.pmid: 1907718
references.citation: J Neurooncol. 2011 Nov;105(2):159-63
references.pmid: 21499727
references.citation: Traffic. 2006 May;7(5):604-12
references.pmid: 16643282
references.citation: Hum Mol Genet. 2002 Oct 1;11(21):2673-87
references.pmid: 12354792
references.citation: Oncol Rep. 2011 Nov;26(5):1337-42
references.pmid: 21822541
references.citation: Science. 2012 Jan 6;335(6064):93-6
references.pmid: 22223806
references.citation: Curr Opin Neurol. 2004 Apr;17(2):205-9
references.pmid: 15021250
references.citation: Curr Opin Cell Biol. 1998 Oct;10(5):594-601
references.pmid: 9818169
references.citation: Traffic. 2000 Dec;1(12):963-75
references.pmid: 11208086
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695
references.citation: Ann Neurol. 2004 Jul;56(1):143-8
references.pmid: 15236414
references.citation: Nature. 1991 Jan 24;349(6307):293-9
references.pmid: 1987490
references.citation: Curr Opin Cell Biol. 1999 Oct;11(5):602-7
references.pmid: 10508656
references.citation: Physiol Rev. 2002 Apr;82(2):291-329
references.pmid: 11917091
references.citation: J Biol Chem. 1996 Dec 20;271(51):33105-9
references.pmid: 8955158
references.citation: J Biol Chem. 2003 May 2;278(18):15457-60
references.pmid: 12556455
references.citation: Hum Mol Genet. 2003 Mar 1;12(5):527-34
references.pmid: 12588800
references.citation: Biochem J. 2011 Jun 1;436(2):447-55
references.pmid: 21361872
references.citation: J Biol Chem. 2001 Feb 16;276(7):5152-65
references.pmid: 11042173
references.citation: Gene. 2007 Oct 1;400(1-2):82-8
references.pmid: 17629635
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12954-9
references.pmid: 11606722
references.citation: Cell. 2009 Oct 16;139(2):337-51
references.pmid: 19837035
references.citation: Nature. 2002 Jul 25;418(6896):417-22
references.pmid: 12140558
references.citation: Biochemistry. 2008 Dec 23;47(51):13647-58
references.pmid: 19035836
references.citation: FEBS Lett. 2005 Aug 29;579(21):4792-6
references.pmid: 16098969
references.citation: Eukaryot Cell. 2008 Feb;7(2):310-8
references.pmid: 18083825
references.citation: Science. 1985 Jun 14;228(4705):1315-7
references.pmid: 4001944
references.citation: Science. 2010 Jan 1;327(5961):88-92
references.pmid: 20044576
references.citation: Dev Cell. 2008 Apr;14(4):523-34
references.pmid: 18410729
references.citation: J Biol Chem. 2012 Nov 16;287(47):39564-77
references.pmid: 23027862
references.citation: Clin Cancer Res. 2010 Apr 15;16(8):2229-34
references.pmid: 20354134
references.citation: J Cell Biol. 1993 Aug;122(4):809-23
references.pmid: 8349731
references.citation: Science. 2008 Jul 18;321(5887):404-7
references.pmid: 18635803
references.citation: J Biol Chem. 2012 Mar 16;287(12):9560-7
references.pmid: 22270369
references.citation: Science. 2013 Aug 23;341(6148):896-9
references.pmid: 23929950
references.citation: Dev Cell. 2001 Nov;1(5):717-24
references.pmid: 11709191
references.citation: J Biol Chem. 2009 Apr 24;284(17):11279-84
references.pmid: 19244252