title: Centriolar satellite- and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly.
abstract: Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the centrosome is unknown. hMsd1/SSX2IP localizes to both the centrosome and centriolar satellites and is required for tethering microtubules to the centrosome. Here we show that hMsd1/SSX2IP-mediated microtubule anchoring is essential for proper centriole assembly and duplication. On hMsd1/SSX2IP knockdown, the centriolar satellites become stuck at the microtubule minus end near the centrosome. Intriguingly, these satellites contain many proteins that normally localize to the centrosome. Of importance, microtubule structures, albeit not being anchored properly, are still required for the emergence of abnormal satellites, as complete microtubule depolymerization results in the disappearance of these aggregates from the vicinity of the centrosome. We highlighted, using superresolution and electron microscopy, that under these conditions, centriole structures are faulty. Remarkably, these cells are insensitive to Plk4 overproduction-induced ectopic centriole formation, yet they accelerate centrosome reduplication upon hydroxyurea arrest. Finally, the appearance of satellite aggregates is cancer cell specific. Together our findings provide novel insights into the mechanism of centriole assembly and microtubule anchoring.
authors.affiliation: The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hori
authors.affiliation: The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Peddie
authors.affiliation: The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Collinson
authors.affiliation: The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom takashi.toda@crick.ac.uk.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D018797:Cell Cycle Proteins; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C000605616:SSX2IP protein, human
references.citation: J Cell Biol. 1973 May;57(2):551-65
references.pmid: 4121290
references.citation: Nat Cell Biol. 2007 Jun;9(6):646-53
references.pmid: 17486116
references.citation: J Cell Biol. 2013 Jul 8;202(1):81-95
references.pmid: 23816619
references.citation: Biochem Biophys Res Commun. 2007 Nov 23;363(3):462-5
references.pmid: 17904521
references.citation: Nature. 2010 Apr 1;464(7289):721-7
references.pmid: 20360735
references.citation: Mol Cells. 2009 Feb 28;27(2):135-42
references.pmid: 19277494
references.citation: Dev Cell. 2009 May;16(5):649-60
references.pmid: 19460342
references.citation: Dev Cell. 2013 Jun 24;25(6):555-71
references.pmid: 23769972
references.citation: Curr Opin Cell Biol. 2002 Feb;14(1):25-34
references.pmid: 11792541
references.citation: J Ultrastruct Res. 1978 Jun;63(3):287-307
references.pmid: 79660
references.citation: J Cell Biol. 2002 Sep 30;158(7):1171-81
references.pmid: 12356862
references.citation: Dev Cell. 2007 Aug;13(2):203-13
references.pmid: 17681132
references.citation: Mol Biol Cell. 2014 Feb;25(4):495-507
references.pmid: 24356449
references.citation: Nat Cell Biol. 2012 Nov;14(11):1148-58
references.pmid: 23086237
references.citation: Dev Cell. 2014 Mar 10;28(5):497-507
references.pmid: 24561039
references.citation: J Cell Biol. 2010 Nov 15;191(4):731-9
references.pmid: 21059844
references.citation: Eur J Cell Biol. 2011 Dec;90(12):983-9
references.pmid: 21945726
references.citation: J Cell Physiol. 2010 Nov;225(2):454-65
references.pmid: 20458743
references.citation: Mol Biol Cell. 2012 Sep;23(17):3322-35
references.pmid: 22767577
references.citation: Nat Commun. 2013;4:1531
references.pmid: 23443559
references.citation: Philos Trans R Soc Lond B Biol Sci. 2014 Sep 5;369(1650). pii: 20130467. doi: 10.1098/rstb.2013.0467
references.pmid: 25047621
references.citation: J Cell Biol. 2005 Nov 7;171(3):437-45
references.pmid: 16275750
references.citation: Curr Biol. 2014 Mar 17;24(6):664-70
references.pmid: 24613305
references.citation: Cell. 1991 May 31;65(5):825-36
references.pmid: 1840506
references.citation: J Cell Biol. 1998 Jun 29;141(7):1563-74
references.pmid: 9647649
references.citation: J Cell Biol. 2007 Oct 22;179(2):321-30
references.pmid: 17954613
references.citation: EMBO Rep. 2014 Feb;15(2):175-84
references.pmid: 24397932
references.citation: J Cell Sci. 2012 Oct 15;125(Pt 20):4770-9
references.pmid: 22797915
references.citation: Nat Rev Mol Cell Biol. 2012 Jul;13(7):425-35
references.pmid: 22691849
references.citation: Dev Cell. 2007 Aug;13(2):190-202
references.pmid: 17681131
references.citation: Mol Cell Biol. 2009 Apr;29(7):1760-73
references.pmid: 19139275
references.citation: Biol Open. 2012 Oct 15;1(10):965-76
references.pmid: 23213374
references.citation: J Cell Sci. 2007 Jul 15;120(Pt 14):2444-53
references.pmid: 17606999
references.citation: Cell. 2007 Jun 15;129(6):1201-13
references.pmid: 17574030
references.citation: J Cell Sci. 2011 Feb 15;124(Pt 4):600-12
references.pmid: 21266464
references.citation: J Cell Biol. 1995 Jul;130(1):105-15
references.pmid: 7790366
references.citation: Methods Enzymol. 2013;525:371-93
references.pmid: 23522479
references.citation: Nat Protoc. 2007;2(10):2480-91
references.pmid: 17947990
references.citation: Nat Cell Biol. 2011 Oct;13(10):1154-60
references.pmid: 21968988
references.citation: Curr Biol. 2014 Oct 6;24(19):2327-34
references.pmid: 25220058
references.citation: PLoS One. 2013;8(3):e58589
references.pmid: 23554904
references.citation: J Cell Biol. 2010 Nov 15;191(4):721-9
references.pmid: 21059850
references.citation: J Cell Biol. 2002 Oct 28;159(2):255-66
references.pmid: 12403812
references.citation: Nature. 2013 Oct 10;502(7470):254-7
references.pmid: 24089205
references.citation: Cell Mol Life Sci. 2015 Jan;72(1):11-23
references.pmid: 25173771
references.citation: J Cell Biol. 1999 Nov 29;147(5):969-80
references.pmid: 10579718
references.citation: Curr Biol. 2010 Sep 28;20(18):R816-25
references.pmid: 20869612
references.citation: EMBO Rep. 2000 Dec;1(6):524-9
references.pmid: 11263498
references.citation: J Cell Biol. 1994 Mar;124(5):783-93
references.pmid: 8120099
references.citation: Hum Mol Genet. 2008 Dec 1;17(23):3796-805
references.pmid: 18772192
references.citation: PLoS One. 2012;7(10):e48196
references.pmid: 23110211
references.citation: Dev Cell. 2002 Sep;3(3):339-50
references.pmid: 12361598