title: PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.
abstract: In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, 433 Biotechnology Building, Ithaca, NY 14853, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Beatty
authors.forename: Diane G
authors.initials: DG
authors.lastname: Morton
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kemphues
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D034622:RNA Interference
chemical_list: C547940:CGEF-1 protein, C elegans; C547941:CHIN-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C553666:LGL-1 protein, C elegans; C081779:cdc-42 protein, C elegans; C087977:par-2 protein, C elegans; C512642:par-6 protein, C elegans; D019204:GTP-Binding Proteins; D009218:Myosins
references.citation: J Cell Biol. 2011 May 2;193(3):583-94
references.pmid: 21518794
references.citation: Development. 1999 Jan;126(1):127-35
references.pmid: 9834192
references.citation: Dev Cell. 2006 Feb;10(2):199-208
references.pmid: 16459299
references.citation: Mol Biol Cell. 2010 Jan 15;21(2):266-77
references.pmid: 19923324
references.citation: Development. 2003 Apr;130(7):1255-65
references.pmid: 12588843
references.citation: Science. 2011 Nov 25;334(6059):1137-41
references.pmid: 22021673
references.citation: Development. 2011 Mar;138(5):799-809
references.pmid: 21303844
references.citation: Dev Biol. 2008 Sep 15;321(2):368-78
references.pmid: 18652816
references.citation: Cell. 2008 Oct 3;135(1):161-73
references.pmid: 18854163
references.citation: Cell. 1988 Feb 12;52(3):311-20
references.pmid: 3345562
references.citation: Gene. 2001 Jan 24;263(1-2):103-12
references.pmid: 11223248
references.citation: Nat Cell Biol. 2006 Sep;8(9):978-85
references.pmid: 16921365
references.citation: Curr Biol. 2001 Apr 3;11(7):482-8
references.pmid: 11412997
references.citation: Genetics. 1995 Nov;141(3):977-88
references.pmid: 8582641
references.citation: Development. 2010 Dec;137(23):3995-4004
references.pmid: 21041363
references.citation: Genetics. 1995 Feb;139(2):549-59
references.pmid: 7713417
references.citation: Curr Biol. 2001 Apr 3;11(7):474-81
references.pmid: 11412996
references.citation: Nature. 2010 Sep 30;467(7315):617-21
references.pmid: 20852613
references.citation: Dev Biol. 2010 Apr 1;340(1):88-98
references.pmid: 20122916
references.citation: Dev Cell. 2004 Sep;7(3):413-24
references.pmid: 15363415
references.citation: Curr Biol. 2010 Jul 27;20(14):1296-303
references.pmid: 20579886
references.citation: Dev Cell. 2009 Jun;16(6):889-900
references.pmid: 19531359
references.citation: Development. 2003 Nov;130(22):5339-50
references.pmid: 13129846
references.citation: Development. 2006 Sep;133(18):3507-16
references.pmid: 16899536
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Biophys J. 2011 Sep 21;101(6):1412-22
references.pmid: 21943422
references.citation: Dev Biol. 2006 Nov 15;299(2):386-97
references.pmid: 16996049
references.citation: Development. 1996 Oct;122(10):3075-84
references.pmid: 8898221
references.citation: Development. 1996 Oct;122(10):3133-40
references.pmid: 8898226
references.citation: Curr Biol. 2004 May 25;14(10):851-62
references.pmid: 15186741
references.citation: Development. 2009 Sep;136(18):3109-19
references.pmid: 19675126