FBW7 couples structural integrity with functional output of primary cilia.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
13 09 2021
13 09 2021
Historique:
received:
05
01
2021
accepted:
30
07
2021
entrez:
14
9
2021
pubmed:
15
9
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Structural defects in primary cilia have robust effects in diverse tissues and systems. However, how disorders of ciliary length lead to functional outcomes are unknown. We examined the functional role of a ciliary length control mechanism of FBW7-mediated destruction of NDE1, in mesenchymal stem cell (MSC) differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on primary cilia formation, MSC differentiation to osteoblasts, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are partially rescued in Fbxw7/Nde1-null cells. We also show that NDE1, despite suppressing ciliogenesis, promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that FBW7 controls a protein-protein interaction network coupling ciliary structure and function, which is essential for stem cell differentiation.
Identifiants
pubmed: 34518642
doi: 10.1038/s42003-021-02504-4
pii: 10.1038/s42003-021-02504-4
pmc: PMC8438042
doi:
Substances chimiques
F-Box-WD Repeat-Containing Protein 7
0
Fbxw7 protein, mouse
0
Microtubule-Associated Proteins
0
Nde1 protein, mouse
0
Types de publication
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.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1066Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK059599
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121656
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR064211
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : DK121656
Organisme : BLRD VA
ID : I01 BX003453
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122259
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126705
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR066262
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : DK059599
Organisme : BLRD VA
ID : IK6 BX004835
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR064211
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Stem Cells. 2012 Nov;30(11):2561-70
pubmed: 22969057
Nat Rev Mol Cell Biol. 2013 Jul;14(7):416-29
pubmed: 23719536
Curr Biol. 2009 Jul 14;19(13):R526-35
pubmed: 19602418
Genes Dev. 2004 Oct 1;18(19):2404-17
pubmed: 15371327
Br J Cancer. 2014 Sep 9;111(6):1054-9
pubmed: 24853181
J Orthop Res. 1991 Sep;9(5):641-50
pubmed: 1870029
EMBO J. 2015 Oct 1;34(19):2388-90
pubmed: 26269527
Nat Genet. 2011 Jul 03;43(8):776-84
pubmed: 21725307
Biochem Biophys Res Commun. 1990 Oct 15;172(1):295-9
pubmed: 1699539
Calcif Tissue Int. 2009 Jan;84(1):56-64
pubmed: 19052794
Cell Rep. 2014 Nov 6;9(3):1099-109
pubmed: 25437563
Dis Model Mech. 2011 Jan;4(1):43-56
pubmed: 21045211
Front Cell Dev Biol. 2021 Feb 09;9:627429
pubmed: 33634128
Mol Biol Cell. 2011 Dec;22(23):4694-703
pubmed: 21976698
Hum Mol Genet. 2005 Aug 1;14(15):2181-8
pubmed: 15994174
Scientifica (Cairo). 2013;2013:684736
pubmed: 24416618
Development. 2009 Feb;136(4):655-64
pubmed: 19144723
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3338-45
pubmed: 14766969
Biochem Biophys Res Commun. 1997 Aug 18;237(2):465-9
pubmed: 9268735
Genes Dev. 2006 May 15;20(10):1365-77
pubmed: 16702409
J Cell Biol. 2016 Feb 15;212(4):409-23
pubmed: 26880200
Am J Med Genet A. 2019 Jun;179(6):1053-1057
pubmed: 30912300
Nat Rev Mol Cell Biol. 2011 Apr;12(4):222-34
pubmed: 21427764
Mol Biol Cell. 2007 Nov;18(11):4365-76
pubmed: 17761537
Mol Cell Biol. 2010 Apr;30(8):1910-22
pubmed: 20154143
Nature. 2010 Aug 12;466(7308):829-34
pubmed: 20703299
J Leukoc Biol. 2012 Jul;92(1):123-31
pubmed: 22493080
J Cell Biol. 2015 Jul 6;210(1):115-33
pubmed: 26150391
Mol Cell Biol. 2005 Sep;25(17):7812-27
pubmed: 16107726
Semin Cell Dev Biol. 2014 Sep;33:63-72
pubmed: 24845016
Cell Commun Signal. 2011 May 14;9:12
pubmed: 21569606
N Engl J Med. 2011 Apr 21;364(16):1533-43
pubmed: 21506742
Elife. 2015 Sep 19;4:
pubmed: 26386247
Nat Commun. 2016 Aug 24;7:12551
pubmed: 27553190
Am J Hum Genet. 2020 Jun 4;106(6):779-792
pubmed: 32413283
Nat Cell Biol. 2011 Apr;13(4):351-60
pubmed: 21394081
Trends Cell Biol. 2017 Feb;27(2):126-140
pubmed: 27634431
EMBO J. 2015 Oct 1;34(19):2424-40
pubmed: 26206584
Blood. 2004 Mar 1;103(5):1662-8
pubmed: 14592819
Oncol Lett. 2019 Mar;17(3):3041-3047
pubmed: 30867732
PLoS Genet. 2005 Oct;1(4):e53
pubmed: 16254602
Curr Opin Cell Biol. 2016 Apr;39:84-92
pubmed: 26926036
Nat Rev Cancer. 2008 Feb;8(2):83-93
pubmed: 18094723
J Cell Biol. 2002 Apr 15;157(2):303-14
pubmed: 11956231
J Orthop Translat. 2014 Aug 27;3(1):26-33
pubmed: 30035037
Cell Mol Life Sci. 2017 Mar;74(5):881-890
pubmed: 27669693
Nat Rev Nephrol. 2019 Apr;15(4):199-219
pubmed: 30733609
Dev Biol. 2017 Sep 1;429(1):147-157
pubmed: 28673820
Am J Hum Genet. 2011 Jul 15;89(1):94-110
pubmed: 21763481
Nature. 2003 Nov 6;426(6962):83-7
pubmed: 14603322
Cell Rep. 2014 Jan 16;6(1):168-181
pubmed: 24373970
Mol Cell. 2016 Feb 4;61(3):419-433
pubmed: 26774286
PLoS One. 2013;8(3):e59354
pubmed: 23555021
Life Sci Alliance. 2020 Jul 10;3(9):
pubmed: 32651191
Dev Biol. 2005 Feb 1;278(1):35-48
pubmed: 15649459
Nat Rev Mol Cell Biol. 2017 Sep;18(9):533-547
pubmed: 28698599
J Cell Biochem. 2003 Aug 15;89(6):1235-49
pubmed: 12898521
Nat Genet. 2016 Apr;48(4):398-406
pubmed: 26950094
Sci Rep. 2018 Feb 16;8(1):3178
pubmed: 29453334
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):
pubmed: 27881449
J Cell Physiol. 2015 Apr;230(4):922-9
pubmed: 25215620
J Cell Biol. 2014 Jan 20;204(2):215-29
pubmed: 24421332
Ther Adv Musculoskelet Dis. 2012 Apr;4(2):61-76
pubmed: 22870496
Development. 2005 Jan;132(1):49-60
pubmed: 15576404