title: A meiosis-specific form of the APC/C promotes the oocyte-to-embryo transition by decreasing levels of the Polo kinase inhibitor matrimony.
abstract: Oocytes are stockpiled with proteins and mRNA that are required to drive the initial mitotic divisions of embryogenesis. But are there proteins specific to meiosis whose levels must be decreased to begin embryogenesis properly? The Drosophila protein Cortex (Cort) is a female, meiosis-specific activator of the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. We performed immunoprecipitation of Cortex followed by mass spectrometry, and identified the Polo kinase inhibitor Matrimony (Mtrm) as a potential interactor with Cort. In vitro binding assays showed Mtrm and Cort can bind directly. We found Mtrm protein levels to be reduced dramatically during the oocyte-to-embryo transition, and this downregulation did not take place in cort mutant eggs, consistent with Mtrm being a substrate of APC(Cort). We showed that Mtrm is subject to APC(Cort)-mediated proteasomal degradation and have identified a putative APC/C recognition motif in Mtrm that when mutated partially stabilized the protein in the embryo. Furthermore, overexpression of Mtrm in the early embryo caused aberrant nuclear divisions and developmental defects, and these were enhanced by decreasing levels of active Polo. These data indicate APC(Cort) ubiquitylates Mtrm at the oocyte-to-embryo transition, thus preventing excessive inhibition of Polo kinase activity due to Mtrm's presence.
authors.affiliation: Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Whitfield
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chisholm
authors.forename: R Scott
authors.initials: RS
authors.lastname: Hawley
authors.forename: Terry L
authors.initials: TL
authors.lastname: Orr-Weaver
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D064199:Cdc20 Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008540:Meiosis; D009865:Oocytes / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C577503:cort protein, Drosophila; C531345:mtrm protein, Drosophila; D064173:Anaphase-Promoting Complex-Cyclosome; C072004:polo protein, Drosophila; D017346:Protein Serine-Threonine Kinases
references.citation: Nat Rev Cancer. 2006 Apr;6(4):321-30
references.pmid: 16557283
references.citation: EMBO Rep. 2003 Dec;4(12):1175-81
references.pmid: 14634695
references.citation: PLoS Biol. 2007 Dec;5(12):e323
references.pmid: 18052611
references.citation: Genes Dev. 2002 Jul 1;16(13):1672-81
references.pmid: 12101125
references.citation: J Cell Biol. 2006 Sep 11;174(6):791-801
references.pmid: 16966421
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):E1222-31
references.pmid: 23479640
references.citation: Development. 1993 Jan;117(1):359-76
references.pmid: 8223258
references.citation: J Vis Exp. 2010 Jun 03;(40):
references.pmid: 20543772
references.citation: Nature. 2007 Apr 26;446(7139):1096-9
references.pmid: 17410129
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14548-53
references.pmid: 11114178
references.citation: PLoS Genet. 2007 Nov;3(11):e202
references.pmid: 18020708
references.citation: Curr Biol. 1998 Feb 12;8(4):243-6
references.pmid: 9501989
references.citation: Mol Biol Cell. 2011 Feb 1;22(3):315-26
references.pmid: 21118994
references.citation: J Cell Sci. 1996 Jul;109 ( Pt 7):1707-15
references.pmid: 8832393
references.citation: Development. 1997 Sep;124(18):3543-53
references.pmid: 9342047
references.citation: Cold Spring Harb Perspect Biol. 2011 Oct 01;3(10):a005553
references.pmid: 21709181
references.citation: Genetics. 1989 Jan;121(1):101-17
references.pmid: 2492966
references.citation: Genesis. 2001 Mar;29(3):141-52
references.pmid: 11252055
references.citation: J Cell Biol. 2010 Aug 23;190(4):501-9
references.pmid: 20733051
references.citation: Genetics. 2003 Oct;165(2):637-52
references.pmid: 14573476
references.citation: Anal Chem. 2002 Oct 15;74(20):5383-92
references.pmid: 12403597
references.citation: Trends Cell Biol. 2004 Aug;14(8):420-6
references.pmid: 15308208
references.citation: J Cell Sci. 2000 Sep;113 ( Pt 18):3341-50
references.pmid: 10954431
references.citation: Cell. 2012 Oct 26;151(3):603-18
references.pmid: 23101628
references.citation: Cell. 2003 Apr 4;113(1):87-99
references.pmid: 12679037
references.citation: Science. 2012 Oct 26;338(6106):520-4
references.pmid: 23019610
references.citation: Curr Biol. 2004 Dec 29;14(24):2183-96
references.pmid: 15620645
references.citation: Curr Biol. 2004 Dec 29;14(24):2168-82
references.pmid: 15620644
references.citation: J Cell Biol. 2001 May 14;153(4):663-76
references.pmid: 11352929
references.citation: Nature. 2007 Apr 26;446(7139):1100-4
references.pmid: 17410130
references.citation: EMBO J. 1994 May 15;13(10):2399-410
references.pmid: 8194530
references.citation: PLoS Genet. 2007 Nov;3(11):e200
references.pmid: 17997611
references.citation: Dev Dyn. 2008 Mar;237(3):527-44
references.pmid: 18265018
references.citation: Nat Rev Mol Cell Biol. 2011 Jun 02;12(7):427-38
references.pmid: 21633387
references.citation: Annu Rev Cell Dev Biol. 2008;24:475-99
references.pmid: 18598214
references.citation: Development. 2007 Mar;134(5):891-9
references.pmid: 17251266
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11217-22
references.pmid: 12169670
references.citation: Mol Cell. 2005 May 27;18(5):543-53
references.pmid: 15916961
references.citation: Mol Cell. 2008 May 9;30(3):290-302
references.pmid: 18471975
references.citation: Dev Biol. 1994 Oct;165(2):299-335
references.pmid: 7958403
references.citation: Development. 1992 Oct;116(2):405-16
references.pmid: 1286615
references.citation: Mol Cell. 2011 Jun 24;42(6):744-57
references.pmid: 21700221
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11990-5
references.pmid: 11050230
references.citation: G3 (Bethesda). 2011 Dec;1(7):607-13
references.pmid: 22384372
references.citation: Genetics. 1998 Sep;150(1):119-28
references.pmid: 9725834
references.citation: J Biol Chem. 2007 Jul 6;282(27):19710-5
references.pmid: 17493939
references.citation: Anal Chem. 2003 Sep 1;75(17):4646-58
references.pmid: 14632076
references.citation: Genetics. 2000 Aug;155(4):1831-9
references.pmid: 10924478
references.citation: Nat Cell Biol. 2010 Jul;12(7):686-95
references.pmid: 20581839
references.citation: Dev Genet. 1992;13(6):440-67
references.pmid: 1304424
references.citation: PLoS Genet. 2012;8(5):e1002667
references.pmid: 22589731
references.citation: J Cell Sci. 2001 Jun;114(Pt 11):2135-43
references.pmid: 11493649
references.citation: EMBO J. 2000 Sep 1;19(17):4513-23
references.pmid: 10970845
references.citation: Genes Dev. 2002 Jul 1;16(13):1659-71
references.pmid: 12101124
references.citation: Curr Biol. 2006 Jan 10;16(1):56-62
references.pmid: 16338136
references.citation: Nat Rev Mol Cell Biol. 2009 Apr;10(4):265-75
references.pmid: 19305416