Myocardin-related transcription factor and serum response factor regulate cilium turnover by both transcriptional and local mechanisms.

cell biology functional aspects of cell biology organizational aspects of cell biology

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
23 Jul 2021
Historique:
received: 12 07 2020
revised: 02 11 2020
accepted: 15 06 2021
entrez: 19 7 2021
pubmed: 20 7 2021
medline: 20 7 2021
Statut: epublish

Résumé

Turnover of the primary cilium (PC) is critical for proliferation and tissue homeostasis. Each key component of the PC resorption machinery, the HEF1/Aurora kinase A (AurA)/HDAC6 pathway harbors cis-elements potentially targeted by the transcriptional co-activator myocardin-related transcription factor (MRTF) and/or its partner serum response factor (SRF). Thus we investigated if MRTF and/or SRF regulate PC turnover. Here we show that (1) both MRTF and SRF are indispensable for serum-induced PC resorption, and (2) they act via both transcriptional and local mechanisms. Intriguingly, MRTF and SRF are present in the basal body and/or the PC, and serum facilitates ciliary MRTF recruitment. MRTF promotes the stability and ciliary accumulation of AurA and facilitates SRF phosphorylation. Ciliary SRF interacts with AurA and HDAC6. MRTF also inhibits ciliogenesis. It interacts with and is required for the correct localization of the ciliogenesis modulator CEP290. Thus, MRTF and SRF are critical regulators of PC assembly and/or disassembly, acting both as transcription factors and as PC constituents.

Identifiants

pubmed: 34278253
doi: 10.1016/j.isci.2021.102739
pii: S2589-0042(21)00707-0
pmc: PMC8261663
doi:

Types de publication

Journal Article

Langues

eng

Pagination

102739

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

Références

Cilia. 2015 Dec 29;4:12
pubmed: 26719793
Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3):
pubmed: 27793968
Circ Res. 2010 Jul 23;107(2):294-304
pubmed: 20558820
J Physiol Pharmacol. 2002 Jun;53(2):147-57
pubmed: 12120892
J Hepatol. 2015 Jan;62(1):165-74
pubmed: 25109772
Organogenesis. 2014 Jan 1;10(1):138-57
pubmed: 24786986
Science. 2004 Oct 29;306(5697):885-8
pubmed: 15514162
Mol Biol Cell. 2008 Apr;19(4):1540-7
pubmed: 18256283
Oncogene. 2007 Oct 11;26(46):6593-603
pubmed: 17452972
Theranostics. 2020 Jan 1;10(4):1719-1732
pubmed: 32042332
EMBO J. 2002 Dec 16;21(24):6820-31
pubmed: 12486003
Mol Cell Biol. 2003 Sep;23(18):6597-608
pubmed: 12944485
Cell Cycle. 2011 Aug 15;10(16):2683-90
pubmed: 21814045
Science. 2014 Jan 10;343(6167):200-4
pubmed: 24408437
Cell Cycle. 2013 Jun 1;12(11):1762-72
pubmed: 23656782
Sci Rep. 2019 Mar 13;9(1):4323
pubmed: 30867502
Nat Cell Biol. 2012 Mar 04;14(4):431-7
pubmed: 22388888
Mol Biol Cell. 2012 Jul;23(14):2658-70
pubmed: 22621899
PLoS Genet. 2016 Feb 09;12(2):e1005785
pubmed: 26859289
Genesis. 2016 Sep;54(9):457-69
pubmed: 27389733
Hum Mol Genet. 2013 Oct 1;22(19):3858-68
pubmed: 23716571
Sci Rep. 2019 Feb 4;9(1):1116
pubmed: 30718762
Mol Cancer Res. 2014 Dec;12(12):1779-95
pubmed: 25061104
J Cell Biol. 2018 Sep 3;217(9):3255-3266
pubmed: 29945904
Biochem Biophys Res Commun. 2018 Feb 5;496(2):450-454
pubmed: 29337054
EMBO J. 2009 Feb 4;28(3):183-92
pubmed: 19153612
Nat Cell Biol. 2013 Jun;15(6):591-601
pubmed: 23644468
Nat Cell Biol. 2011 Apr;13(4):402-11
pubmed: 21394082
J Biol Chem. 2010 Jul 16;285(29):22036-49
pubmed: 20466732
Nat Commun. 2015 Apr 07;6:6781
pubmed: 25849865
Sci Rep. 2017 Nov 10;7(1):15248
pubmed: 29127365
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2932-7
pubmed: 20133761
Front Oncol. 2016 Jan 18;5:307
pubmed: 26835416
Genes Dev. 2014 May 1;28(9):943-58
pubmed: 24732378
Dev Cell. 2008 Aug;15(2):187-97
pubmed: 18694559
Elife. 2016 Jun 15;5:
pubmed: 27304076
Nat Rev Mol Cell Biol. 2019 Jul;20(7):389-405
pubmed: 30948801
Front Cell Dev Biol. 2020 Dec 17;8:622822
pubmed: 33392209
Mol Biol Cell. 2014 Mar;25(5):643-57
pubmed: 24403605
J Mol Cell Cardiol. 2003 Jun;35(6):577-93
pubmed: 12788374
Dev Dyn. 2018 Mar;247(3):396-404
pubmed: 28681541
Hum Mutat. 2010 Oct;31(10):1097-108
pubmed: 20690115
Mol Cell. 2016 Dec 15;64(6):1048-1061
pubmed: 27867007
Curr Rheumatol Rep. 2019 May 21;21(6):29
pubmed: 31115730
J Cardiovasc Transl Res. 2012 Dec;5(6):794-804
pubmed: 22898751
Cell. 2017 Jan 12;168(1-2):264-279.e15
pubmed: 28086093
J Cell Sci. 2013 Mar 15;126(Pt 6):1355-65
pubmed: 23345402
Nature. 2004 Mar 11;428(6979):185-9
pubmed: 15014501
Nat Commun. 2012;3:1055
pubmed: 22968701
Cell. 2003 May 2;113(3):329-42
pubmed: 12732141
Biochem J. 2007 Apr 1;403(1):119-27
pubmed: 17125467
Am J Pathol. 2018 Jan;188(1):11-22
pubmed: 29030052
J Biol Chem. 2002 Nov 22;277(47):45558-65
pubmed: 12244051
Trends Cell Biol. 2017 Feb;27(2):126-140
pubmed: 27634431
J Cell Biol. 2018 Mar 5;217(3):929-944
pubmed: 29321169
J Biol Chem. 2017 Sep 8;292(36):14902-14920
pubmed: 28739802
Oncol Lett. 2019 Mar;17(3):3041-3047
pubmed: 30867732
Mol Biol Cell. 2007 Mar;18(3):1083-97
pubmed: 17215519
Circulation. 2019 May 14;139(20):2342-2357
pubmed: 30818997
Semin Cell Dev Biol. 2017 Nov;71:42-52
pubmed: 28843978
Nat Genet. 2011 Jul 03;43(8):776-84
pubmed: 21725307
Mol Biol Cell. 2018 Jul 1;29(13):1611-1627
pubmed: 29742020
Am J Physiol Cell Physiol. 2007 Jan;292(1):C70-81
pubmed: 16928770
Sci Rep. 2015 Aug 06;5:12917
pubmed: 26246421
Cell. 2007 Jun 29;129(7):1351-63
pubmed: 17604723
Nat Protoc. 2006;1(3):1458-61
pubmed: 17406435
Nat Rev Mol Cell Biol. 2010 May;11(5):353-65
pubmed: 20414257
EMBO J. 2012 May 18;31(14):3104-17
pubmed: 22609948
J Biol Chem. 2011 Dec 23;286(51):44116-44125
pubmed: 22049076
Nat Cell Biol. 2016 Jun 28;18(7):711-7
pubmed: 27350441
Semin Cell Dev Biol. 2020 Jun;102:132-138
pubmed: 31862221
Cell. 2015 Dec 3;163(6):1484-99
pubmed: 26638075
Hum Mol Genet. 2008 Dec 1;17(23):3796-805
pubmed: 18772192
Nat Rev Nephrol. 2019 Apr;15(4):199-219
pubmed: 30733609
Am J Physiol Renal Physiol. 2003 May;284(5):F911-24
pubmed: 12505862
Diabetes Metab J. 2018 Apr;42(2):117-127
pubmed: 29676541
J Cell Biol. 2018 Aug 6;217(8):2831-2849
pubmed: 29945903
J Cell Biol. 2010 Oct 18;191(2):303-12
pubmed: 20956379
Am J Physiol Lung Cell Mol Physiol. 2014 May 1;306(9):L829-39
pubmed: 24610937
Nat Rev Cancer. 2018 Aug;18(8):511-524
pubmed: 29802351
Development. 2018 Sep 17;145(18):
pubmed: 30224385
Nat Commun. 2016 May 18;7:11642
pubmed: 27189435
J Biol Chem. 2001 May 18;276(20):17206-12
pubmed: 11278806
Nat Rev Mol Cell Biol. 2017 Sep;18(9):533-547
pubmed: 28698599
Circ Res. 2011 Apr 29;108(9):1093-101
pubmed: 21393577
Dev Cell. 2007 May;12(5):767-78
pubmed: 17488627
Nat Commun. 2015 Aug 20;6:8087
pubmed: 26290419
J Cell Biol. 2010 Feb 8;188(3):383-99
pubmed: 20123992
Front Genet. 2019 Mar 11;10:127
pubmed: 30915099
J Am Soc Nephrol. 2009 Oct;20(10):2104-11
pubmed: 19762494
Cell. 1999 Jul 23;98(2):159-69
pubmed: 10428028
Mol Cell Biol. 2006 Jun;26(11):4134-48
pubmed: 16705166
Annu Rev Cell Dev Biol. 2010;26:59-87
pubmed: 19575670
Mol Cells. 2018 Mar 31;41(3):224-233
pubmed: 29477141

Auteurs

Pam Speight (P)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.

Matthew Rozycki (M)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.

Shruthi Venugopal (S)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.

Katalin Szászi (K)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.
Department of Surgery, University of Toronto, Toronto, ON M5B 1T8, Canada.

Michael Kofler (M)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.

András Kapus (A)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada.
Department of Surgery, University of Toronto, Toronto, ON M5B 1T8, Canada.
Department of Biochemistry, University of Toronto, Toronto, ON M5B 1T8, Canada.

Classifications MeSH