title: Ran GTPase promotes oocyte polarization by regulating ERM (Ezrin/Radixin/Moesin) inactivation.
abstract: Asymmetric meiotic divisions in mammalian oocytes are driven by the eccentric positioning of the spindle, along with a dramatic reorganization of the overlying cortex, including a loss of microvilli and formation of a thick actin cap. Actin polarization relies on a Ran-GTP gradient centered on metaphase chromosomes; however, the downstream signaling cascade is not completely understood. In a recent study, we have shown that Ran promotes actin cap formation via the polarized activation of Cdc42. The related GTPase Rac is also activated in a polarized fashion in the oocyte cortex and co-localizes with active Cdc42. In other cells, microvilli collapse can be triggered by inactivation of the ERM (Ezrin/Radixin/Moesin) family of actin-membrane crosslinkers under the control of Rac. Accordingly, we show here that Ran-GTP promotes a substantial loss of phosphorylated ERMs in the cortex overlying the spindle in mouse oocytes. However, this polarized phospho-ERM exclusion zone was unaffected by Rac or Cdc42 inhibition. Therefore, we suggest that Ran activates two distinct pathways to regulate actin cap formation and microvilli disassembly in the polarized cortex of mouse oocytes. The possibility of a crosstalk between Rho GTPase and ERM signaling and a role for ERM inactivation in promoting cortical actin dynamics are also discussed.
authors: Institut de Génétique et Développement de Rennes, CNRS UMR 6290; Rennes, France.
authors: Benoit
authors: B
authors: Dehapiot
authors: Guillaume
authors: G
authors: Halet
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008540:Meiosis; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D020764:cdc42 GTP-Binding Protein; D020931:ran GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin
keywords: GTPase; actin; chromatin; meiosis; oocyte; polarity
references: Curr Biol. 2012 Feb 7;22(3):231-6
references: 22209527
references: Curr Biol. 2011 Feb 22;21(4):270-7
references: 21295482
references: J Cell Biol. 2004 Mar 1;164(5):653-9
references: 14993232
references: Cytoskeleton (Hoboken). 2012 Oct;69(10):727-37
references: 22753278
references: J Embryol Exp Morphol. 1986 Apr;93:213-38
references: 3734683
references: Blood. 2012 Jan 12;119(2):445-53
references: 22106344
references: J Cell Biol. 2009 Feb 9;184(3):451-62
references: 19204146
references: Acta Crystallogr D Biol Crystallogr. 2001 Jun;57(Pt 6):889-90
references: 11375519
references: Nat Rev Mol Cell Biol. 2010 Apr;11(4):276-87
references: 20308985
references: PLoS One. 2010 Aug 25;5(8):e12393
references: 20811629
references: Exp Cell Res. 2012 Jul 15;318(12):1442-7
references: 22406266
references: Mol Biol Cell. 2010 Sep 15;21(18):3182-92
references: 20660156
references: Dev Biol. 1998 Aug 1;200(1):103-15
references: 9698460
references: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):10946-51
references: 21690351
references: Nat Cell Biol. 2011 Aug 28;13(10):1252-8
references: 21874009
references: Curr Top Dev Biol. 1978;12:83-105
references: 352627
references: Nat Immunol. 2004 Mar;5(3):272-9
references: 14758359
references: Dev Biol. 2007 Apr 1;304(1):317-25
references: 17239847
references: Dev Cell. 2007 Feb;12(2):309-17
references: 17276347
references: J Immunol. 2004 Oct 15;173(8):4985-93
references: 15470041
references: J Cell Sci. 2012 Jul 15;125(Pt 14):3310-9
references: 22467863
references: Blood. 2003 Dec 1;102(12):3890-9
references: 12907449
references: Nature. 2002 Dec 12;420(6916):629-35
references: 12478284
references: J Cell Biol. 2007 Jan 29;176(3):295-305
references: 17261848
references: Curr Biol. 2008 Dec 23;18(24):1986-92
references: 19062278
references: Dev Biol. 2013 May 1;377(1):202-12
references: 23384564
references: Curr Biol. 2008 Oct 14;18(19):1514-9
references: 18848445
references: J Embryol Exp Morphol. 1986 Mar;92:11-32
references: 3723057
references: Cell. 2003 Feb 21;112(4):453-65
references: 12600310
references: Dev Biol. 1996 Aug 1;177(2):568-79
references: 8806832
references: J Cell Biol. 2000 Jan 10;148(1):127-36
references: 10629223
references: J Cell Biol. 1999 Jun 28;145(7):1497-509
references: 10385528
references: Nat Rev Mol Cell Biol. 2013 Mar;14(3):141-52
references: 23429793
references: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7495-9
references: 7638219
references: J Cell Biol. 2011 Oct 3;195(1):99-112
references: 21969469
references: Exp Cell Res. 2007 Apr 1;313(6):1106-20
references: 17292355
references: J Cell Sci. 2002 May 15;115(Pt 10):2139-49
references: 11973355
references: J Cell Biol. 1999 Nov 29;147(5):1009-22
references: 10579721
references: J Cell Biol. 2008 Sep 8;182(5):827-36
references: 18762580
references: Mol Reprod Dev. 2009 Sep;76(9):819-31
references: 19363790
references: Hum Reprod Update. 2011 Jan-Feb;17(1):68-75
references: 20833637
references: J Biol Chem. 1997 Sep 12;272(37):23371-5
references: 9287351
references: Dev Biol. 1985 Feb;107(2):382-94
references: 4038667
references: J Cell Biol. 1997 Nov 3;139(3):749-58
references: 9348291
references: J Cell Biol. 2013 Mar 4;200(5):567-76
references: 23439682
references: Dev Cell. 2007 Feb;12(2):301-8
references: 17276346
references: Annu Rev Cell Biol. 1993;9:411-44
references: 8280467