title: Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis.
abstract: SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval-pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpression of Snmp1 is able to recover lipid droplet levels in the smt3 knockdown prothoracic gland cells. Snmp1 expression depends on Ftz-f1 (an NR5A-type orphan nuclear receptor), the expression of which, in turn, depends on SUMO. Furthermore, we show by in vitro and in vivo experiments that Ftz-f1 is SUMOylated. RNAi-mediated knockdown of ftz-f1 phenocopies that of smt3 at the larval to pupal transition, thus Ftz-f1 is an interesting candidate to mediate some of the functions of SUMO at the onset of metamorphosis. Additionally, we demonstrate that the role of SUMOylation, Ftz-f1, and the Scavenger Receptors in lipid capture and mobilization is conserved in other steroidogenic tissues such as the follicle cells of the ovary. smt3 knockdown, as well as ftz-f1 or Scavenger knockdown, depleted the lipid content of the follicle cells, which could be rescued by Snmp1 overexpression. Therefore, our data provide new insights into the regulation of metamorphosis via lipid homeostasis, showing that Drosophila Smt3, Ftz-f1, and SR-BIs are part of a general mechanism for uptake of lipids such as cholesterol, required during development in steroidogenic tissues.
authors: CIC bioGUNE, Derio, Bizkaia, Spain. atalamillo@cicbiogune.es
authors: Ana
authors: A
authors: Talamillo
authors: Leire
authors: L
authors: Herboso
authors: Lucia
authors: L
authors: Pirone
authors: Coralia
authors: C
authors: Pérez
authors: Monika
authors: M
authors: González
authors: Jonatan
authors: J
authors: Sánchez
authors: Ugo
authors: U
authors: Mayor
authors: Fernando
authors: F
authors: Lopitz-Otsoa
authors: Manuel S
authors: MS
authors: Rodriguez
authors: James D
authors: JD
authors: Sutherland
authors: Rosa
authors: R
authors: Barrio
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D008969:Molecular Sequence Data; D051116:Receptors, Scavenger; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051116:Receptors, Scavenger; D014157:Transcription Factors
references: Mol Endocrinol. 1997 Feb;11(2):127-37
references: 9013760
references: Curr Biol. 1998 Nov 19;8(23):1277-80
references: 9822580
references: Gene Expr Patterns. 2009 Jan;9(1):50-3
references: 18755298
references: J Lipid Res. 2002 Apr;43(4):544-9
references: 11907136
references: Cell Metab. 2009 Dec;10(6):481-90
references: 19945405
references: PLoS Genet. 2011 Feb 10;7(2):e1001297
references: 21347279
references: Biochem Soc Trans. 2006 Dec;34(Pt 6):1256-60
references: 17073797
references: Trends Endocrinol Metab. 2003 Dec;14(10):467-72
references: 14643062
references: Mol Cell Endocrinol. 2009 Mar 5;300(1-2):83-8
references: 18840501
references: Curr Biol. 2005 Oct 25;15(20):1796-807
references: 16182527
references: J Morphol. 1972 May;137(1):29-48
references: 4338127
references: Mol Cell Biol. 2010 Feb;30(3):793-805
references: 19933845
references: Development. 2011 Jun;138(12):2477-85
references: 21561986
references: Biochim Biophys Acta. 2005 Sep 5;1736(1):10-29
references: 16099208
references: Endocrinology. 1998 Jun;139(6):2847-56
references: 9607793
references: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10
references: 15897460
references: Dev Dyn. 2006 Feb;235(2):315-26
references: 16273522
references: Dev Biol. 2010 Aug 15;344(2):1100-9
references: 20678979
references: Nutr Metab (Lond). 2006 Dec 15;3:43
references: 17173681
references: Development. 2007 Oct;134(20):3733-42
references: 17804599
references: Mol Cell Biol. 2005 Mar;25(5):1879-90
references: 15713642
references: Development. 1997 May;124(9):1757-69
references: 9165123
references: J Insect Physiol. 1977;23(1):109-19
references: 858928
references: Nat Med. 2008 Jun;14(6):656-66
references: 18500350
references: Mol Cell Endocrinol. 2007 Feb;265-266:42-5
references: 17208360
references: Biochem Soc Trans. 2010 Feb;38(Pt 1):54-9
references: 20074035
references: Biochem J. 2011 Jan 1;433(1):155-61
references: 20950277
references: Genes Cells. 1997 Sep;2(9):559-69
references: 9413997
references: Mol Cell. 2002 Oct;10(4):831-42
references: 12419227
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13773-8
references: 14610274
references: Biochim Biophys Acta. 2011 Aug;1812(8):909-18
references: 21172431
references: Science. 1997 Apr 4;276(5309):114-7
references: 9082981
references: Nature. 2008 May 29;453(7195):657-61
references: 18408709
references: Nutr Metab (Lond). 2010 Jun 01;7:47
references: 20515451
references: J Biol Chem. 2004 Sep 10;279(37):38730-5
references: 15192092
references: Insect Biochem Mol Biol. 2004 Sep;34(9):991-1010
references: 15350618
references: Genesis. 2002 Sep-Oct;34(1-2):51-7
references: 12324947
references: J Biol Chem. 2004 Oct 15;279(42):43805-14
references: 15294908
references: J Biol Chem. 1998 Nov 27;273(48):32353-9
references: 9822716
references: Cell Metab. 2010 Oct 6;12(4):398-410
references: 20889131
references: Int J Biochem Cell Biol. 2004 Jan;36(1):39-77
references: 14592533
references: Insect Biochem Mol Biol. 2008 Apr;38(4):430-9
references: 18342248
references: J Cell Biol. 2005 Nov 7;171(3):549-58
references: 16260500
references: Development. 2006 Jul;133(13):2565-74
references: 16763204
references: J Lipid Res. 1999 Oct;40(10):1799-805
references: 10508199
references: Cell Tissue Res. 1983;229(2):433-41
references: 6850754
references: Nature. 2007 Nov 8;450(7167):289-93
references: 17943085
references: Development. 2000 Oct;127(19):4115-26
references: 10976044
references: Biol Bull. 1976 Jun;150(3):500-21
references: 953075
references: J Biol Chem. 2003 May 9;278(19):16809-19
references: 12615929
references: Mol Cell. 2005 Apr 1;18(1):1-12
references: 15808504
references: Cell. 2010 Apr 30;141(3):536-48
references: 20434990
references: Mol Endocrinol. 2004 Oct;18(10):2451-62
references: 15192080
references: J Cell Biol. 1999 Feb 8;144(3):533-47
references: 9971747
references: Biochim Biophys Acta. 2011 Jul;1814(7):900-7
references: 21545853
references: Immunity. 1996 May;4(5):431-43
references: 8630729
references: Nat Methods. 2007 Mar;4(3):245-50
references: 17277783
references: Biochem Biophys Res Commun. 2009 Jan 16;378(3):513-7
references: 19041634
references: J Neuroinflammation. 2009 Mar 26;6:12
references: 19323834
references: J Biol Chem. 2003 Aug 29;278(35):33416-21
references: 12810706
references: Science. 1982 Oct 22;218(4570):341-7
references: 6289435
references: Mol Cell Endocrinol. 2007 Feb;265-266:174-8
references: 17196738
references: Dev Cell. 2001 Oct;1(4):453-65
references: 11703937
references: PLoS One. 2012;7(2):e32086
references: 22348149
references: Endocrinology. 1999 Dec;140(12):5669-81
references: 10579331
references: Development. 2010 Jan;137(1):123-31
references: 20023167
references: Mol Endocrinol. 2005 Nov;19(11):2671-84
references: 15961505
references: Development. 2008 May;135(9):1659-68
references: 18367553
references: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13728-33
references: 16950879
references: Dev Biol. 2003 May 1;257(1):153-65
references: 12710964
references: FEBS J. 2009 Jan;276(2):425-36
references: 19125815
references: Cell Tissue Res. 1991 Sep;265(3):435-45
references: 1786592
references: Mol Cell Endocrinol. 2002 Sep 30;195(1-2):1-26
references: 12354669
references: Dev Biol. 1982 Sep;93(1):73-82
references: 6813165
references: Biochem Soc Trans. 2008 Oct;36(Pt 5):868-73
references: 18793153
references: Mol Biol Cell. 2009 Oct;20(19):4235-45
references: 19692572
references: J Biol Chem. 1997 Dec 26;272(52):33068-76
references: 9407090
references: Mol Cell. 2005 Feb 18;17(4):491-502
references: 15721253
references: Genetics. 2006 Jan;172(1):185-96
references: 16079224
references: Cell. 2005 Feb 11;120(3):343-55
references: 15707893
references: J Cell Sci. 2006 Mar 15;119(Pt 6):1184-95
references: 16507588
references: Dev Biol. 2005 Jun 1;282(1):84-94
references: 15936331
references: Mol Cell. 1999 Feb;3(2):143-9
references: 10078197
references: Mol Endocrinol. 1999 Sep;13(9):1460-73
references: 10478838
references: Development. 2005 Nov;132(22):5115-24
references: 16221727
references: J Neurobiol. 2001 Oct;49(1):47-61
references: 11536197
references: Mol Cell Proteomics. 2011 May;10(5):M110.002188
references: 20861518
references: Dev Dyn. 2008 Nov;237(11):3179-91
references: 18816439
references: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3312-7
references: 17360644
references: Cell Metab. 2009 Mar;9(3):228-39
references: 19254568
references: Mol Cell Endocrinol. 1982 Apr;26(1-2):51-80
references: 7084564
references: Science. 2005 Oct 28;310(5748):667-70
references: 16179433
references: PLoS One. 2009 Jun 16;4(6):e5905
references: 19529778
references: Cell Mol Life Sci. 2011 Dec;68(24):4045-64
references: 21892772
references: Development. 2000 Dec;127(23):5083-92
references: 11060234
references: J Biol Chem. 2000 Dec 29;275(52):40765-76
references: 10995744
references: Sci Rep. 2011;1:75
references: 22355594
references: Mol Cell Biol. 2010 May;30(9):2135-46
references: 20194620
references: Dev Cell. 2011 Aug 16;21(2):315-27
references: 21820362
references: Development. 1999 Oct;126(20):4591-602
references: 10498693
references: Methods Mol Biol. 2009;497:3-16
references: 19107407
references: Mol Cell Biol. 2007 Dec;27(23):8330-9
references: 17908794
references: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1613-8
references: 11171999
references: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3004-8
references: 8096644
references: Mol Cell Biol. 2000 Feb;20(3):1072-82
references: 10629064
references: Genes Dev. 2009 Dec 1;23(23):2711-6
references: 19952106
references: Int J Dev Biol. 2011;55(6):603-11
references: 21948708
references: J Endocrinol. 2002 Dec;175(3):663-72
references: 12475377
references: Mol Cell Biol. 2008 Dec;28(24):7476-86
references: 18838537
references: Mol Endocrinol. 2000 Jan;14(1):66-81
references: 10628748
references: Mol Cell Endocrinol. 2004 Feb 27;215(1-2):1-10
references: 15026169
references: J Biol Chem. 2010 Aug 13;285(33):25841-9
references: 20562097
references: Insect Biochem Mol Biol. 2008 Apr;38(4):398-415
references: 18342246
references: Genes Dev. 2011 Jul 15;25(14):1476-85
references: 21715559