title: Proteomic and functional analysis of the mitotic Drosophila centrosome.
abstract: Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. As part of these pathways, numerous proteins with well-established non-centrosomal localization and function associate with the centrosome to fulfill regulatory functions. In turn, classical centrosomal components take up functional and structural roles as part of other cellular organelles and compartments. Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. We analysed the Drosophila embryonic centrosomal proteome using immunoisolation in combination with mass spectrometry. The 251 identified components were functionally characterized by RNA interference. Among those, a core group of 11 proteins was critical for centrosome structure maintenance. Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin- and RNA-binding proteins. In total, we assigned novel centrosome-related functions to 24 proteins and confirmed 13 of these in human cells.
authors.affiliation: Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Müller
authors.forename: David
authors.initials: D
authors.lastname: Schmidt
authors.forename: Sandra
authors.initials: S
authors.lastname: Steinbrink
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Mirgorodskaya
authors.forename: Verena
authors.initials: V
authors.lastname: Lehmann
authors.forename: Karin
authors.initials: K
authors.lastname: Habermann
authors.forename: Felix
authors.initials: F
authors.lastname: Dreher
authors.forename: Niklas
authors.initials: N
authors.lastname: Gustavsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Kessler
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Ralf
authors.initials: R
authors.lastname: Herwig
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.forename: Aspasia
authors.initials: A
authors.lastname: Ploubidou
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.forename: Bodo M H
authors.initials: BM
authors.lastname: Lange
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000737:chemistry* / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000737:chemistry* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000502:physiology; D013058:Mass Spectrometry; D008938:Mitosis / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D034622:RNA Interference
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone
references.citation: Trends Cell Biol. 1993 Apr;3(4):118-28
references.pmid: 14731766
references.citation: Genes Dev. 1999 Jun 1;13(11):1422-37
references.pmid: 10364159
references.citation: Oncogene. 2008 Nov 24;27(55):6994-7002
references.pmid: 19029940
references.citation: Proteomics. 2004 Sep;4(9):2707-21
references.pmid: 15352245
references.citation: J Cell Biol. 2009 Nov 2;187(3):355-63
references.pmid: 19948479
references.citation: Genes Dev. 2001 May 15;15(10):1167-81
references.pmid: 11358861
references.citation: Curr Biol. 2008 Feb 26;18(4):303-9
references.pmid: 18291647
references.citation: Nat Rev Mol Cell Biol. 2001 Sep;2(9):688-98
references.pmid: 11533726
references.citation: J Cell Biol. 1995 Sep;130(5):1149-59
references.pmid: 7657699
references.citation: PLoS Biol. 2008 Apr 22;6(4):e98
references.pmid: 18433294
references.citation: J Cell Biol. 1998 May 18;141(4):967-77
references.pmid: 9585415
references.citation: J Cell Sci. 2004 Apr 15;117(Pt 10):1911-22
references.pmid: 15090595
references.citation: Dev Biol. 2010 Apr 15;340(2):408-18
references.pmid: 20122915
references.citation: Development. 2004 Feb;131(4):863-71
references.pmid: 14736750
references.citation: Nature. 2004 Feb 19;427(6976):753-7
references.pmid: 14973490
references.citation: J Cell Biol. 2008 Feb 25;180(4):681-9
references.pmid: 18283114
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2950-5
references.pmid: 9501196
references.citation: Cell. 2006 May 5;125(3):523-33
references.pmid: 16678096
references.citation: Curr Opin Cell Biol. 2002 Feb;14(1):25-34
references.pmid: 11792541
references.citation: J Cell Sci. 1996 Dec;109 ( Pt 13):3001-12
references.pmid: 9004035
references.citation: Curr Biol. 2007 Sep 4;17(17):1465-72
references.pmid: 17689959
references.citation: J Cell Biol. 1999 Feb 22;144(4):721-33
references.pmid: 10037793
references.citation: J Cell Biol. 2000 Jul 24;150(2):F37-44
references.pmid: 10908584
references.citation: Mol Cell Biol. 2008 Mar;28(5):1755-69
references.pmid: 18172010
references.citation: Mol Cell Biol. 1998 Jun;18(6):3540-51
references.pmid: 9584194
references.citation: Gene. 2004 Feb 4;326:107-16
references.pmid: 14729268
references.citation: Neuron. 2003 Sep 25;40(1):25-40
references.pmid: 14527431
references.citation: J Cell Biol. 1985 Jan;100(1):35-46
references.pmid: 3880758
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D175-80
references.pmid: 18971254
references.citation: J Cell Sci. 1997 Feb;110 ( Pt 4):451-64
references.pmid: 9067597
references.citation: J Cell Biol. 2010 Feb 8;188(3):313-23
references.pmid: 20123993
references.citation: EMBO J. 2000 Mar 15;19(6):1252-62
references.pmid: 10716925
references.citation: Mol Biol Cell. 2009 May;20(10):2605-14
references.pmid: 19321663
references.citation: Nat Rev Genet. 2005 Mar;6(3):194-205
references.pmid: 15738963
references.citation: J Cell Biol. 2003 Dec 22;163(6):1197-204
references.pmid: 14691132
references.citation: Curr Biol. 2007 Oct 23;17(20):1735-45
references.pmid: 17935995
references.citation: J Biol Chem. 2004 Apr 2;279(14):13721-8
references.pmid: 14739278
references.citation: Cell. 2005 Apr 22;121(2):223-34
references.pmid: 15851029
references.citation: Mol Cell Biol. 1996 Dec;16(12):6870-8
references.pmid: 8943342
references.citation: J Cell Biol. 2004 Jun 7;165(5):673-83
references.pmid: 15184400
references.citation: J Biol Chem. 2009 Apr 3;284(14):9418-25
references.pmid: 19201755
references.citation: J Cell Biol. 2001 Apr 2;153(1):237-42
references.pmid: 11285289
references.citation: Nat Rev Cancer. 2002 Nov;2(11):815-25
references.pmid: 12415252
references.citation: Nat Cell Biol. 2001 Jul;3(7):643-9
references.pmid: 11433296
references.citation: Curr Opin Cell Biol. 2002 Feb;14(1):35-43
references.pmid: 11792542
references.citation: J Gen Virol. 2005 Mar;86(Pt 3):589-594
references.pmid: 15722518
references.citation: Biochem Biophys Res Commun. 2002 Aug 16;296(2):288-92
references.pmid: 12163015
references.citation: Curr Protoc Cell Biol. 2006 Jan;Chapter 3:Unit 3.17
references.pmid: 18228485
references.citation: Nat Cell Biol. 2001 Jan;3(1):68-75
references.pmid: 11146628
references.citation: Curr Biol. 2009 Jun 9;19(11):937-42
references.pmid: 19427213
references.citation: Trends Cell Biol. 2009 Jul;19(7):325-33
references.pmid: 19576775
references.citation: Genes Dev. 2008 Aug 15;22(16):2189-203
references.pmid: 18662975
references.citation: Science. 2006 Oct 27;314(5799):654-7
references.pmid: 17068266
references.citation: J Cell Sci. 2007 Dec 15;120(Pt 24):4321-31
references.pmid: 18042621
references.citation: Oncogene. 2002 Sep 9;21(40):6209-21
references.pmid: 12214251
references.citation: EMBO J. 2010 Feb 17;29(4):843-54
references.pmid: 20111006
references.citation: Genes Dev. 2000 Dec 15;14(24):3126-39
references.pmid: 11124805
references.citation: Curr Biol. 2007 Oct 23;17(20):1759-64
references.pmid: 17919907
references.citation: Nature. 2008 Dec 18;456(7224):971-5
references.pmid: 19011615
references.citation: Nat Rev Mol Cell Biol. 2007 Jun;8(6):451-63
references.pmid: 17505520
references.citation: Cell. 1996 May 17;85(4):585-96
references.pmid: 8653793
references.citation: J Cell Sci. 1994 Apr;107 ( Pt 4):859-67
references.pmid: 8056842
references.citation: Development. 1999 Jul;126(13):2829-39
references.pmid: 10357928
references.citation: J Cell Biol. 2006 Feb 13;172(4):517-28
references.pmid: 16476773
references.citation: J Cell Biol. 1989 Dec;109(6 Pt 1):2869-78
references.pmid: 2592409
references.citation: Nature. 2003 Dec 4;426(6966):570-4
references.pmid: 14654843
references.citation: Nat Cell Biol. 2010 Feb;12(2):164-9
references.pmid: 20081840
references.citation: Genes Dev. 1998 May 15;12(10):1483-94
references.pmid: 9585508
references.citation: J Cell Sci. 2005 Nov 15;118(Pt 22):5381-92
references.pmid: 16280552
references.citation: J Cell Biol. 2000 Jul 24;150(2):F51-6
references.pmid: 10908586
references.citation: Proteomics. 2005 Feb;5(2):399-408
references.pmid: 15648048
references.citation: J Cell Biol. 1995 Dec;131(5):1261-73
references.pmid: 8522588
references.citation: PLoS Genet. 2008 Jul 18;4(7):e1000126
references.pmid: 18797514
references.citation: Nat Cell Biol. 2007 Dec;9(12):1401-12
references.pmid: 17994010
references.citation: Mol Biol Cell. 1995 Nov;6(11):1563-74
references.pmid: 8589456
references.citation: Genes Dev. 2008 Jan 1;22(1):91-105
references.pmid: 18086858
references.citation: Science. 1966 Feb 25;151(3713):992-5
references.pmid: 5907291
references.citation: Cell. 2006 Jun 30;125(7):1375-86
references.pmid: 16814722
references.citation: Methods Cell Biol. 1999;61:35-56
references.pmid: 9891308
references.citation: Science. 2004 Feb 6;303(5659):832-5
references.pmid: 14764878
references.citation: Genetics. 2009 May;182(1):133-44
references.pmid: 19293139
references.citation: EMBO Rep. 2009 Jun;10(6):606-13
references.pmid: 19390532
references.citation: Nat Cell Biol. 2005 Oct;7(10):937-46
references.pmid: 16184168
references.citation: J Cell Biol. 2007 Aug 27;178(5):725-32
references.pmid: 17709428
references.citation: Mol Biol Cell. 2006 Jan;17(1):272-82
references.pmid: 16236791
references.citation: EMBO J. 2000 Jan 17;19(2):241-52
references.pmid: 10637228
references.citation: Science. 2007 Apr 20;316(5823):417-21
references.pmid: 17412918
references.citation: Curr Top Dev Biol. 2000;49:343-63
references.pmid: 11005027
references.citation: Genetics. 2008 Dec;180(4):2081-94
references.pmid: 18854586
references.citation: Science. 2007 May 18;316(5827):1046-50
references.pmid: 17463247
references.citation: PLoS Biol. 2008 Sep 16;6(9):e224
references.pmid: 18798690
references.citation: Development. 2002 Dec;129(24):5553-66
references.pmid: 12421697
references.citation: EMBO J. 2000 Aug 1;19(15):3932-44
references.pmid: 10921875
references.citation: Nat Cell Biol. 2000 Feb;2(2):90-5
references.pmid: 10655588
references.citation: Curr Top Dev Biol. 2000;49:449-70
references.pmid: 11005031
references.citation: Curr Biol. 2005 Jun 21;15(12):1090-8
references.pmid: 15964273
references.citation: Curr Biol. 2002 Aug 6;12(15):1287-92
references.pmid: 12176356
references.citation: Mol Biol Cell. 2004 Jan;15(1):37-45
references.pmid: 14565985
references.citation: J Cell Sci. 1997 Jul;110 ( Pt 13):1431-40
references.pmid: 9224761
references.citation: J Virol. 2006 Jun;80(12):5807-21
references.pmid: 16731920
references.citation: Cell. 2004 May 14;117(4):541-52
references.pmid: 15137946