title: Drosophila Hephaestus/polypyrimidine tract binding protein is required for dorso-ventral patterning and regulation of signalling between the germline and soma.
abstract: In the Drosophila oocyte, gurken (grk) mRNA encodes a secreted TGF-α signal that specifies the future embryonic dorso-ventral axes by altering the fate of the surrounding epithelial follicle cells. We previously identified a number of RNA binding proteins that associate specifically with the 64 nucleotide grk localization signal, including the Drosophila orthologue of polypyrimidine tract-binding protein (PTB), Hephaestus (Heph). To test whether Heph is required for correct grk mRNA or protein function, we used immunoprecipitation to validate the association of Heph with grk mRNA and characterized the heph mutant phenotype. We found that Heph is a component of grk mRNP complexes but heph germline clones show that Heph is not required for grk mRNA localization. Instead, we identify a novel function for Heph in the germline and show that it is required for proper Grk protein localization. Furthermore, we show that Heph is required in the oocyte for the correct organization of the actin cytoskeleton and dorsal appendage morphogenesis. Our results highlight a requirement for an mRNA binding protein in the localization of Grk protein, which is independent of mRNA localization, and we propose that Heph is required in the germline for efficient Grk signalling to the somatic follicle cells during dorso-ventral patterning.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom. suzanne.mcdermott@seattlebiomed.org
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: McDermott
authors.forename: Ilan
authors.initials: I
authors.lastname: Davis
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D019521:Body Patterning; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000378:metabolism*; D008297:Male; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C588105:Heph protein, Drosophila; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; D038941:Polypyrimidine Tract-Binding Protein
references.citation: Curr Opin Cell Biol. 2002 Aug;14(4):428-33
references.pmid: 12383793
references.citation: Dev Biol. 2009 Apr 1;328(1):160-72
references.pmid: 19389362
references.citation: Nature. 1992 Jul 30;358(6385):387-92
references.pmid: 1641021
references.citation: Science. 2005 Sep 23;309(5743):2054-7
references.pmid: 16179478
references.citation: Development. 1993 Dec;119(4):1359-69
references.pmid: 8306893
references.citation: Development. 2009 Feb;136(4):551-61
references.pmid: 19144719
references.citation: Biol Cell. 2005 Jan;97(1):19-33
references.pmid: 15601255
references.citation: Cell. 1995 Jun 16;81(6):967-78
references.pmid: 7540118
references.citation: Development. 2007 Oct;134(19):3419-25
references.pmid: 17827179
references.citation: Genetics. 1996 Dec;144(4):1673-9
references.pmid: 8978054
references.citation: Curr Opin Genet Dev. 1999 Aug;9(4):396-404
references.pmid: 10449356
references.citation: Nature. 2008 May 1;453(7191):115-9
references.pmid: 18451862
references.citation: Development. 2006 Feb;133(3):459-70
references.pmid: 16396907
references.citation: Mol Cell Biol. 1999 Jan;19(1):78-85
references.pmid: 9858533
references.citation: J Cell Sci. 2008 Mar 15;121(Pt 6):887-94
references.pmid: 18303053
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1894-9
references.pmid: 20133837
references.citation: EMBO J. 2003 Jun 16;22(12):2924-33
references.pmid: 12805208
references.citation: Dev Cell. 2007 Oct;13(4):539-53
references.pmid: 17925229
references.citation: Mol Cell Biol. 2006 Dec;26(24):9508-16
references.pmid: 17030623
references.citation: Nature. 1994 May 26;369(6478):315-8
references.pmid: 7514276
references.citation: Cell. 2009 Feb 20;136(4):719-30
references.pmid: 19239891
references.citation: Biochim Biophys Acta. 2007 Jun;1773(6):912-23
references.pmid: 17400307
references.citation: Genes Dev. 1989 Dec;3(12A):1874-86
references.pmid: 2533575
references.citation: Dev Biol. 2013 Jan 15;373(2):349-58
references.pmid: 23127433
references.citation: Dev Cell. 2005 Jul;9(1):51-62
references.pmid: 15992540
references.citation: Dev Cell. 2006 Aug;11(2):251-62
references.pmid: 16890164
references.citation: Science. 1995 May 26;268(5214):1173-6
references.pmid: 7761834
references.citation: Curr Opin Genet Dev. 2011 Dec;21(6):719-25
references.pmid: 21862318
references.citation: Cell Cycle. 2011 Nov 1;10(21):3706-13
references.pmid: 22037210
references.citation: Neuron. 2001 Nov 20;32(4):683-96
references.pmid: 11719208
references.citation: Biol Open. 2012 May 15;1(5):488-97
references.pmid: 23213441
references.citation: PLoS One. 2011;6(7):e21876
references.pmid: 21750738
references.citation: Development. 2007 Apr;134(7):1419-30
references.pmid: 17329360
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12570-5
references.pmid: 20616016
references.citation: Biochem Soc Trans. 2005 Jun;33(Pt 3):457-60
references.pmid: 15916540
references.citation: Genes Dev. 1999 Apr 1;13(7):864-76
references.pmid: 10197986
references.citation: Cell. 2007 Oct 5;131(1):174-87
references.pmid: 17923096
references.citation: Dev Cell. 2003 Mar;4(3):307-19
references.pmid: 12636913
references.citation: PLoS One. 2012;7(3):e33144
references.pmid: 22427970
references.citation: Mol Cell. 1999 Sep;4(3):431-7
references.pmid: 10518224
references.citation: Genes Dev. 2012 Jun 1;26(11):1209-23
references.pmid: 22661231
references.citation: Genetics. 2004 Jun;167(2):707-23
references.pmid: 15238523
references.citation: Mol Cell Biol. 2004 Sep;24(18):7878-90
references.pmid: 15340051
references.citation: RNA. 1997 Jul;3(7):764-78
references.pmid: 9214659
references.citation: Nature. 1995 Jun 22;375(6533):654-8
references.pmid: 7791898
references.citation: Dev Biol. 2009 Feb 15;326(2):327-34
references.pmid: 19100729
references.citation: Genes Dev. 1993 Jun;7(6):948-60
references.pmid: 7684991
references.citation: Cell. 1991 Jul 12;66(1):37-50
references.pmid: 2070417
references.citation: Dev Cell. 2007 Nov;13(5):691-704
references.pmid: 17981137
references.citation: Genes Dev. 2009 Jan 15;23(2):195-207
references.pmid: 19131435
references.citation: J Mol Biol. 2000 Nov 24;304(2):119-33
references.pmid: 11080450
references.citation: Development. 2003 Dec;130(25):6273-82
references.pmid: 14602681
references.citation: Nucleic Acids Res. 2010 Nov;38(20):7068-78
references.pmid: 20576698
references.citation: Mech Dev. 2002 Feb;111(1-2):143-7
references.pmid: 11804786
references.citation: RNA. 2007 Aug;13(8):1214-23
references.pmid: 17592047
references.citation: Curr Diabetes Rev. 2006 Aug;2(3):363-6
references.pmid: 18220641
references.citation: Curr Biol. 2009 Sep 15;19(17):1429-37
references.pmid: 19716703
references.citation: Trends Genet. 2005 Jun;21(6):346-55
references.pmid: 15922834
references.citation: Mol Cell Biol. 2008 Jan;28(2):678-86
references.pmid: 18039852
references.citation: Mol Cell Biol. 2004 May;24(10):4174-83
references.pmid: 15121839
references.citation: PLoS Genet. 2008 Jan;4(1):e8
references.pmid: 18208331
references.citation: Cell. 1987 Jun 5;49(5):699-707
references.pmid: 3107840
references.citation: Cell. 1991 Jul 12;66(1):23-35
references.pmid: 2070416
references.citation: Development. 2008 Jan;135(2):343-51
references.pmid: 18077592
references.citation: Mech Dev. 2008 Jan-Feb;125(1-2):142-52
references.pmid: 18053693
references.citation: J Cell Biol. 2008 Jan 14;180(1):31-8
references.pmid: 18195099
references.citation: Mol Cell. 2003 Mar;11(3):757-71
references.pmid: 12667457
references.citation: Cell. 1993 Oct 8;75(1):165-74
references.pmid: 7691414
references.citation: Development. 1997 Nov;124(22):4639-47
references.pmid: 9409680
references.citation: J Cell Biol. 2007 Dec 31;179(7):1365-73
references.pmid: 18166649
references.citation: Genetics. 1993 Oct;135(2):489-505
references.pmid: 8244010
references.citation: J Mol Biol. 2007 Mar 16;367(1):174-86
references.pmid: 17239394
references.citation: Dev Dyn. 1994 Feb;199(2):103-15
references.pmid: 7515724
references.citation: Mol Cell Biol. 1998 Aug;18(8):4855-62
references.pmid: 9671494
references.citation: Biol Cell. 2005 Jan;97(1):97-110
references.pmid: 15601261
references.citation: Mech Dev. 1996 Oct;59(2):105-13
references.pmid: 8951789
references.citation: Curr Top Dev Biol. 1999;44:203-43
references.pmid: 9891881
references.citation: Dev Biol. 2009 Apr 15;328(2):434-44
references.pmid: 19217894
references.citation: Cell. 1992 Apr 3;69(1):173-84
references.pmid: 1339308
references.citation: Nat Neurosci. 2012 Jan 15;15(3):381-8, S1
references.pmid: 22246437
references.citation: Mol Biol Cell. 2004 Dec;15(12):5306-17
references.pmid: 15385627
references.citation: Curr Opin Cell Biol. 2010 Feb;22(1):112-9
references.pmid: 20022233
references.citation: Curr Biol. 2002 Dec 10;12(23):1971-81
references.pmid: 12477385
references.citation: Mol Cell Biol. 2009 Oct;29(20):5564-77
references.pmid: 19667078
references.citation: Mol Cell Biol. 1999 Apr;19(4):2699-711
references.pmid: 10082536
references.citation: Annu Rev Cell Dev Biol. 1997;13:147-70
references.pmid: 9442871
references.citation: Curr Biol. 2003 Aug 19;13(16):1388-96
references.pmid: 12932322
references.citation: Dev Cell. 2007 Oct;13(4):523-38
references.pmid: 17925228
references.citation: Development. 1995 Sep;121(9):3023-33
references.pmid: 7555728
references.citation: Development. 2002 Dec;129(24):5553-66
references.pmid: 12421697
references.citation: Dev Cell. 2005 Nov;9(5):675-85
references.pmid: 16256742
references.citation: Development. 2004 May;131(9):1949-58
references.pmid: 15056611
references.citation: Science. 2009 Nov 27;326(5957):1212-6
references.pmid: 19965463
references.citation: Nature. 1998 Feb 19;391(6669):792-5
references.pmid: 9486649
references.citation: Fly (Austin). 2009 Jan-Mar;3(1):15-28
references.pmid: 19182536