Bi-allelic mutation in SEC16B alters collagen trafficking and increases ER stress.
SEC16B
autophagy
endoplasmic reticulum
osteogenesis imperfecta
type I collagen
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
11 04 2023
11 04 2023
Historique:
revised:
15
02
2023
received:
02
09
2022
accepted:
17
02
2023
medline:
12
4
2023
pubmed:
15
3
2023
entrez:
14
3
2023
Statut:
ppublish
Résumé
Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder characterized by bone fragility and reduced bone mass generally caused by defects in type I collagen structure or defects in proteins interacting with collagen processing. We identified a homozygous missense mutation in SEC16B in a child with vertebral fractures, leg bowing, short stature, muscular hypotonia, and bone densitometric and histomorphometric features in keeping with OI with distinct ultrastructural features. In line with the putative function of SEC16B as a regulator of trafficking between the ER and the Golgi complex, we showed that patient fibroblasts accumulated type I procollagen in the ER and exhibited a general trafficking defect at the level of the ER. Consequently, patient fibroblasts exhibited ER stress, enhanced autophagosome formation, and higher levels of apoptosis. Transfection of wild-type SEC16B into patient cells rescued the collagen trafficking. Mechanistically, we show that the defect is a consequence of reduced SEC16B expression, rather than due to alterations in protein function. These data suggest SEC16B as a recessive candidate gene for OI.
Identifiants
pubmed: 36916446
doi: 10.15252/emmm.202216834
pmc: PMC10086588
doi:
Substances chimiques
Collagen
9007-34-5
Collagen Type I
0
Procollagen Type I
0
SEC16B protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16834Subventions
Organisme : Austrian Social Health Insurance Fund
Organisme : Austrian Society for Bone and Mineral Research
Organisme : Institutional funds
Organisme : Research funds of the Austrian Workers Compensation Board
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Int J Mol Sci. 2021 Jan 10;22(2):
pubmed: 33435159
Trends Biochem Sci. 2011 Feb;36(2):108-16
pubmed: 20934340
FEBS Lett. 2009 Dec 3;583(23):3796-803
pubmed: 19850039
Nat Methods. 2012 Mar 11;9(5):493-8
pubmed: 22406856
Calcif Tissue Int. 2008 Apr;82(4):263-70
pubmed: 18311573
Biol Open. 2013 Mar 15;2(3):256-66
pubmed: 23519012
J Cell Sci. 2015 Feb 15;128(4):670-82
pubmed: 25526736
Nat Rev Endocrinol. 2011 Jun 14;7(9):540-57
pubmed: 21670757
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Bone Rep. 2021 Jul 26;15:101110
pubmed: 34381850
J Cell Biol. 2017 Jun 5;216(6):1731-1743
pubmed: 28442536
J Biol Chem. 1997 Oct 10;272(41):25413-6
pubmed: 9325247
J Cell Sci. 2008 Sep 15;121(Pt 18):3025-34
pubmed: 18713835
Am J Med Genet A. 2014 Jun;164A(6):1470-81
pubmed: 24715559
J Biol Chem. 2007 Jun 15;282(24):17632-9
pubmed: 17428803
Am J Hum Genet. 2015 Mar 5;96(3):432-9
pubmed: 25683121
J Orthop Res. 2019 Jan;37(1):35-50
pubmed: 30370699
Stain Technol. 1977 Jul;52(4):217-9
pubmed: 71768
Sci Rep. 2011;1:77
pubmed: 22355596
J Bone Miner Res. 1995 Sep;10(9):1410-6
pubmed: 7502714
J Cell Sci. 2009 Aug 15;122(Pt 16):2924-34
pubmed: 19638414
Endocr Rev. 2022 Jan 12;43(1):61-90
pubmed: 34007986
Traffic. 2006 Dec;7(12):1678-87
pubmed: 17005010
JBMR Plus. 2021 Jan 13;5(3):e10451
pubmed: 33778321
Traffic. 2018 Nov;19(11):823-839
pubmed: 29978536
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
J Cell Biol. 1995 Oct;131(2):311-24
pubmed: 7593161
Bone. 2014 Jul;64:82-7
pubmed: 24705007
J Clin Endocrinol Metab. 2010 May;95(5):2418-25
pubmed: 20215397
Bone. 2000 Jun;26(6):581-9
pubmed: 10831929
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12746-51
pubmed: 21768384
Annu Rev Genet. 2012;46:475-97
pubmed: 23145505
Bone. 2000 Feb;26(2):103-9
pubmed: 10678403
Nat Genet. 2006 Oct;38(10):1192-7
pubmed: 16980979
J Biol Chem. 2002 May 31;277(22):19521-9
pubmed: 11912203
J Cell Biol. 2019 Aug 5;218(8):2470-2480
pubmed: 31227593
J Cell Sci. 2005 Apr 1;118(Pt 7):1341-53
pubmed: 15788652
Nutr Diabetes. 2018 Jul 19;8(1):43
pubmed: 30026463
Mol Biol Cell. 2007 Mar;18(3):839-49
pubmed: 17192411
Skeletal Radiol. 2015 Mar;44(3):321-38
pubmed: 25269751
Curr Opin Pediatr. 2014 Aug;26(4):500-7
pubmed: 25007323
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
J Cell Biol. 2010 Jun 14;189(6):997-1011
pubmed: 20548102
Elife. 2020 Feb 26;9:
pubmed: 32101163
J Cell Biol. 2002 Sep 16;158(6):1029-38
pubmed: 12235121
Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12255-E12264
pubmed: 30545919
Mol Biol Cell. 1996 Nov;7(11):1815-23
pubmed: 8930902
Electrophoresis. 2016 Nov;37(22):2922-2929
pubmed: 27461483
Hum Genet. 2021 Aug;140(8):1121-1141
pubmed: 34169326
Nat Genet. 2006 Oct;38(10):1198-203
pubmed: 16980978
Bone. 2009 Jun;44(6):1043-8
pubmed: 19268565
Pharmaceuticals (Basel). 2021 Nov 08;14(11):
pubmed: 34832915