Glycosylation limits forward trafficking of the tetraspan membrane protein PMP22.
Charcot–Marie–Tooth disease (CMTD)
ER quality control
N-linked glycosylation
peripheral myelin protein 22 (PMP22)
peripheral neuropathy
trafficking
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
20
12
2020
revised:
20
04
2021
accepted:
27
04
2021
pubmed:
3
5
2021
medline:
20
8
2021
entrez:
2
5
2021
Statut:
ppublish
Résumé
Peripheral myelin protein 22 (PMP22) folds and trafficks inefficiently, with only 20% of newly expressed protein trafficking to the cell surface. This behavior is exacerbated in many of the mutants associated with Charcot-Marie-Tooth disease, motivating further study. Here we characterized the role of N-glycosylation in limiting PMP22 trafficking. We first eliminated N-glycosylation using an N41Q mutation, which resulted in an almost 3-fold increase in trafficking efficiency of wildtype (WT) PMP22 and a 10-fold increase for the severely unstable L16P disease mutant in HEK293 cells, with similar results in Schwann cells. Total cellular levels were also much higher for the WT/N41Q mutant, although not for the L16P/N41Q form. Depletion of oligosaccharyltransferase OST-A and OST-B subunits revealed that WT PMP22 is N-glycosylated posttranslationally by OST-B, whereas L16P is cotranslationally glycosylated by OST-A. Quantitative proteomic screens revealed similarities and differences in the interactome for WT, glycosylation-deficient, and unstable mutant forms of PMP22 and also suggested that L16P is sequestered at earlier stages of endoplasmic reticulum quality control. CRISPR knockout studies revealed a role for retention in endoplasmic reticulum sorting receptor 1 (RER1) in limiting the trafficking of all three forms, for UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1) in limiting the trafficking of WT and L16P but not N41Q, and calnexin (CNX) in limiting the trafficking of WT and N41Q but not L16P. This work shows that N-glycosylation is a limiting factor to forward trafficking PMP22 and sheds light on the proteins involved in its quality control.
Identifiants
pubmed: 33933451
pii: S0021-9258(21)00508-1
doi: 10.1016/j.jbc.2021.100719
pmc: PMC8191293
pii:
doi:
Substances chimiques
Adaptor Proteins, Vesicular Transport
0
Myelin Proteins
0
PMP22 protein, human
0
RER1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100719Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133552
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095989
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS113494
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM065086
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
Références
J Cell Biol. 1992 Apr;117(1):225-38
pubmed: 1556154
Mol Cell Neurosci. 1997 Jan;9(1):13-25
pubmed: 9204477
Sci Adv. 2018 Mar 07;4(3):eaar2631
pubmed: 29532034
J Biol Chem. 2005 Jan 21;280(3):2378-87
pubmed: 15537650
J Neurosci. 1999 Mar 15;19(6):2027-36
pubmed: 10066256
J Am Chem Soc. 2015 Jul 15;137(27):8758-68
pubmed: 26102530
Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14168-14177
pubmed: 32513719
Biochim Biophys Acta. 2013 Nov;1833(11):2430-7
pubmed: 23583305
Mol Genet Genomic Med. 2014 Nov;2(6):522-9
pubmed: 25614874
Ann Neurol. 2014 Feb;75(2):255-65
pubmed: 24339129
FASEB J. 2011 Nov;25(11):3929-37
pubmed: 21831887
Semin Cell Dev Biol. 2015 May;41:79-89
pubmed: 25534658
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14404-9
pubmed: 11717414
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17182-7
pubmed: 20855604
J Mol Biol. 1987 Dec 20;198(4):655-76
pubmed: 3430624
Annu Rev Cell Dev Biol. 2016 Oct 6;32:197-222
pubmed: 27298089
Nat Cell Biol. 1999 Oct;1(6):330-4
pubmed: 10559958
FEBS J. 2020 Oct;287(20):4322-4340
pubmed: 32285592
Traffic. 2016 Apr;17(4):308-26
pubmed: 26676362
Biochemistry. 2014 Oct 7;53(39):6139-41
pubmed: 25243937
Essays Biochem. 2016 Oct 15;60(2):227-235
pubmed: 27744338
Elife. 2018 May 29;7:
pubmed: 29809151
J Biol Chem. 2019 Aug 9;294(32):12054-12065
pubmed: 31213528
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
J Neurosci. 2014 Nov 26;34(48):16140-52
pubmed: 25429154
J Biol Chem. 2020 Aug 21;295(34):11963-11970
pubmed: 32647009
Cell Chem Biol. 2018 Oct 18;25(10):1231-1241.e4
pubmed: 30078634
Sci Adv. 2017 Jul 05;3(7):e1700220
pubmed: 28695207
J Biol Chem. 1993 May 15;268(14):10372-9
pubmed: 8486695
Q Rev Biophys. 2015 Feb;48(1):1-34
pubmed: 25420508
Curr Opin Neurol. 2017 Oct;30(5):471-480
pubmed: 28678038
Neurobiol Dis. 2004 Nov;17(2):300-9
pubmed: 15474367
Neurobiol Dis. 1999 Oct;6(5):450-60
pubmed: 10527811
Structure. 2011 Aug 10;19(8):1160-9
pubmed: 21827951
Sci Rep. 2016 Feb 11;6:20946
pubmed: 26864433
Mol Biol Cell. 2013 Sep;24(17):2597-608
pubmed: 23864712
Science. 2019 Dec 13;366(6471):1372-1375
pubmed: 31831667
Neurobiol Dis. 1999 Feb;6(1):1-14
pubmed: 10078969
Curr Opin Cell Biol. 2016 Aug;41:57-65
pubmed: 27085638
J Cell Biol. 2019 Oct 7;218(10):3171-3187
pubmed: 31537714
Mol Cell Proteomics. 2020 Dec 8;20:100008
pubmed: 33581410
J Cell Biol. 2008 Feb 25;180(4):705-12
pubmed: 18283111
Mol Biol Cell. 2005 Mar;16(3):1142-51
pubmed: 15635102
Cell. 2009 Jan 23;136(2):272-83
pubmed: 19167329
Hum Mol Genet. 2013 Nov 15;22(22):4638-45
pubmed: 23842455
Chem Rev. 2019 May 8;119(9):5537-5606
pubmed: 30608666
Biochemistry. 2008 Oct 7;47(40):10620-9
pubmed: 18795802
J Neuropathol Exp Neurol. 2003 Jul;62(7):751-64
pubmed: 12901701
Nature. 2014 Feb 6;506(7486):107-10
pubmed: 24499919
Nat Chem Biol. 2016 Dec;12(12):1023-1030
pubmed: 27694802
Crit Rev Biochem Mol Biol. 2019 Apr;54(2):153-163
pubmed: 31084437
Sci Rep. 2014 Nov 11;4:6992
pubmed: 25385046
Mol Neurobiol. 2013 Apr;47(2):673-98
pubmed: 23224996
J Proteome Res. 2012 May 4;11(5):2697-709
pubmed: 22509746
Nat Commun. 2015 Sep 28;6:8403
pubmed: 26411746
Methods. 1997 Jul;12(3):224-34
pubmed: 9237167
Int J Mol Sci. 2019 Jul 12;20(14):
pubmed: 31336816
J Neurosci. 2019 Jul 3;39(27):5404-5418
pubmed: 31061090
Cell. 2014 Jun 19;157(7):1632-43
pubmed: 24930395
Neurobiol Dis. 2000 Dec;7(6 Pt B):561-73
pubmed: 11114256
J Neuropathol Exp Neurol. 2016 Apr;75(4):334-46
pubmed: 26921370
Cell. 2018 Nov 29;175(6):1507-1519.e16
pubmed: 30415835
J Neurosci. 1997 Oct 15;17(20):7754-62
pubmed: 9315897
Structure. 2017 Sep 5;25(9):1415-1422.e3
pubmed: 28877505
Ann Neurol. 1999 Jan;45(1):16-24
pubmed: 9894872
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
Cell Chem Biol. 2019 Jul 18;26(7):913-925.e4
pubmed: 31105062
Prog Brain Res. 1992;94:163-76
pubmed: 1287719
J Cell Biol. 2014 Aug 18;206(4):525-39
pubmed: 25135935
Biochemistry. 2013 May 14;52(19):3229-41
pubmed: 23639031
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
pubmed: 12883005
Mol Cell Neurosci. 2004 Dec;27(4):370-8
pubmed: 15555916
PM R. 2014 Apr;6(4):342-55
pubmed: 24434692
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
J Neurochem. 2000 Oct;75(4):1465-74
pubmed: 10987826
Elife. 2016 Jul 20;5:
pubmed: 27435961
Biochem Biophys Res Commun. 2019 Apr 2;511(2):356-362
pubmed: 30791981
Handb Exp Pharmacol. 2018;245:385-425
pubmed: 29460152
Genetics. 2013 Feb;193(2):383-410
pubmed: 23396477
Mol Cell. 2015 Apr 16;58(2):269-83
pubmed: 25801167
J Cell Biol. 2019 Aug 5;218(8):2782-2796
pubmed: 31296534
Biochim Biophys Acta. 2010 Jun;1803(6):684-93
pubmed: 19891995
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9852-7
pubmed: 12119418