Maintaining the proper connection between the centrioles and the pericentriolar matrix requires Drosophila centrosomin.
Centrosomes consist of two centrioles surrounded by an amorphous pericentriolar matrix (PCM), but it is unknown how centrioles and PCM are connected. We show that the centrioles in Drosophila embryos that lack the centrosomal protein Centrosomin (Cnn) can recruit PCM components but cannot maintain a proper attachment to the PCM. As a result, the centrioles "rocket" around in the embryo and often lose their connection to the nucleus in interphase and to the spindle poles in mitosis. This leads to severe mitotic defects in embryos and to errors in centriole segregation in somatic cells. The Cnn-related protein CDK5RAP2 is linked to microcephaly in humans, but cnn mutant brains are of normal size, and we observe only subtle defects in the asymmetric divisions of mutant neuroblasts. We conclude that Cnn maintains the proper connection between the centrioles and the PCM; this connection is required for accurate centriole segregation in somatic cells but is not essential for the asymmetric division of neuroblasts.
Lucas
Eliana P
EP
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, England, UK.
Raff
Jordan W
JW
D000818:Animals; D001921:Brain / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D018385:Centrosome / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007814:Larva / Q000033:anatomy & histology / Q000378:metabolism; D022101:Microtubule-Organizing Center; D008870:Microtubules / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; C098130:cnn protein, Drosophila
Trends Cell Biol. 2001 Oct;11(10):413-9
11567874
EMBO J. 2001 Apr 2;20(7):1704-14
11285234
Dev Cell. 2002 Nov;3(5):685-96
12431375
J Cell Biol. 2003 Sep 1;162(5):757-63
12939255
Science. 2003 Sep 12;301(5639):1547-50
12970569
Mol Biol Cell. 2004 May;15(5):2287-301
15004232
Curr Biol. 2004 May 4;14(9):763-75
15120067
J Cell Biol. 2004 Jun 7;165(5):673-83
15184400
Development. 1993 Jun;118(2):401-15
8223268
Mech Dev. 1998 Nov;78(1-2):113-8
9858703
EMBO J. 1999 Apr 15;18(8):2184-95
10205172
Development. 1999 Jul;126(13):2829-39
10357928
Curr Biol. 1999 Aug 26;9(16):889-98
10469591
Nat Rev Genet. 2005 Mar;6(3):194-205
15738963
Nat Genet. 2005 Apr;37(4):353-5
15793586
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7847-52
15911773
Annu Rev Cell Dev Biol. 2005;21:411-34
16212501
Curr Biol. 2005 Dec 20;15(24):2199-207
16326102
Curr Opin Cell Biol. 2006 Feb;18(1):95-101
16337370
Curr Biol. 2006 Mar 21;16(6):564-9
16546079
Cell. 2006 Jun 30;125(7):1375-86
16814722
Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10438-43
16798874
Dev Cell. 2006 Jul;11(1):9-19
16824949
Science. 2007 Jan 26;315(5811):518-21
17255513
Dev Cell. 2007 Mar;12(3):467-74
17336911
J Cell Biol. 2007 Apr 9;177(1):13-20
17403931
Curr Biol. 2007 May 15;17(10):834-43
17475495
Curr Opin Cell Biol. 2000 Feb;12(1):104-12
10679366
Development. 2000 Oct;127(19):4253-64
10976056
Nat Cell Biol. 1999 Dec;1(8):493-9
10587645
Nat Cell Biol. 2001 Jul;3(7):643-9
11433296
Curr Biol. 2001 Jan 23;11(2):116-20
11231128
J Biol Chem. 2001 Apr 6;276(14):11189-98
11134006
Annu Rev Biochem. 2001;70:649-76
11395419