The chromosome passenger complex is required for fidelity of chromosome transmission and cytokinesis in meiosis of mouse oocytes.
The existence of two forms of the chromosome passenger complex (CPC) in the mammalian oocyte has meant that its role in female meiosis has remained unclear. Here we use loss- and gain-of function approaches to assess the meiotic functions of one of the shared components of these complexes, INCENP, and of the variable kinase subunits, Aurora B or Aurora C. We show that either the depletion of INCENP or the combined inhibition of Aurora kinases B and C activates the anaphase-promoting complex or cyclosome (APC/C) before chromosomes have properly congressed in meiosis I and also prevents cytokinesis and hence extrusion of the first polar body. Overexpression of Aurora C also advances APC/C activation and results in cytokinesis failure in a high proportion of oocytes, indicative of a dominant effect on CPC function. Together, this points to roles for the meiotic CPC in functions similar to the mitotic roles of the complex: correcting chromosome attachment to microtubules, facilitating the spindle-assembly checkpoint (SAC) function and enabling cytokinesis. Surprisingly, overexpression of Aurora B leads to a failure of APC/C activation, stabilization of securin and consequently a failure of chiasmate chromosomes to resolve - a dominant phenotype that is completely suppressed by depletion of INCENP. Taken together with the differential distribution of Aurora proteins B and C on chiasmate chromosomes, this points to differential functions of the two forms of CPC in regulating the separation of homologous chromosomes in meiosis I.
University of Cambridge, Wellcome Trust and Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge, UK CB2 1NR.
Bedra
B
Sharif
Jie
J
Na
Karin
K
Lykke-Hartmann
Stephen H
SH
McLaughlin
Ernest
E
Laue
David M
DM
Glover
Magdalena
M
Zernicka-Goetz
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000378:metabolism*; D023902:Chromosome Pairing / Q000187:drug effects / Q000235:genetics; D020090:Chromosome Segregation / Q000187:drug effects; D033481:Chromosomes, Mammalian / Q000187:drug effects / Q000378:metabolism*; D048749:Cytokinesis / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005799:Genes, Dominant; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; C513185:Incenp protein, mouse; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C576924:Aurkb protein, mouse; C576928:Aurkc protein, mouse; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases