title: Chitinases and Imaginal disc growth factors organize the extracellular matrix formation at barrier tissues in insects.
abstract: The cuticle forms an apical extracellular-matrix (ECM) that covers exposed organs, such as epidermis, trachea and gut, for organizing morphogenesis and protection of insects. Recently, we reported that cuticle proteins and chitin are involved in ECM formation. However, molecular mechanisms that control assembly, maturation and replacement of the ECM and its components are not well known. Here we investigated the poorly described glyco-18-domain hydrolase family in Drosophila and identified the Chitinases (Chts) and imaginal-disc-growth-factors (Idgfs) that are essential for larval and adult molting. We demonstrate that Cht and idgf depletion results in deformed cuticles, larval and adult molting defects, and insufficient protection against wounding and bacterial infection, which altogether leads to early lethality. We show that Cht2/Cht5/Cht7/Cht9/Cht12 and idgf1/idgf3/idgf4/idgf5/idgf6 are needed for organizing proteins and chitin-matrix at the apical cell surface. Our data indicate that normal ECM formation requires Chts, which potentially hydrolyze chitin-polymers. We further suggest that the non-enzymatic idgfs act as structural proteins to maintain the ECM scaffold against chitinolytic degradation. Conservation of Chts and Idgfs proposes analogous roles in ECM dynamics across the insect taxa, indicating that Chts/Idgfs are new targets for species specific pest control.
authors.affiliation: Institute for Biology and Translational Center for Regenerative Medicine (TRM), University of Leipzig, 04103 Leipzig, Germany.|Life &Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Yanina-Yasmin
authors.initials: YY
authors.lastname: Pesch
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Electron microscopy group, 37077 Göttingen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.affiliation: Life &Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Kapil R
authors.initials: KR
authors.lastname: Patil
authors.affiliation: Life &Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Loch
authors.affiliation: Institute for Biology and Translational Center for Regenerative Medicine (TRM), University of Leipzig, 04103 Leipzig, Germany.|Life &Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Behr
mesh_terms: D000818:Animals; D002688:Chitinases / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000378:metabolism; D018978:Molting / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D002688:Chitinases
references.citation: J Biophys Biochem Cytol. 1961 Aug;10:589-618
references.pmid: 13762980
references.citation: PLoS Genet. 2014 Aug;10(8):e1004537
references.pmid: 25144557
references.citation: Insect Biochem Mol Biol. 2008 Apr;38(4):452-66
references.pmid: 18342250
references.citation: Insect Biochem Mol Biol. 2011 Aug;41(8):521-8
references.pmid: 21419847
references.citation: Development. 2008 Jun;135(12):2055-64
references.pmid: 18480161
references.citation: Insect Biochem Mol Biol. 2010 May;40(5):363-75
references.pmid: 20347980
references.citation: Insect Biochem Mol Biol. 2008 Apr;38(4):467-77
references.pmid: 18342251
references.citation: Exp Cell Res. 2014 Feb 1;321(1):64-70
references.pmid: 24075963
references.citation: Cell Mol Life Sci. 2010 Jan;67(2):201-16
references.pmid: 19816755
references.citation: Curr Biol. 2006 Jan 24;16(2):180-5
references.pmid: 16431370
references.citation: FEBS Lett. 2011 Oct 20;585(20):3316-21
references.pmid: 21945316
references.citation: PLoS One. 2010;5(10):e13477
references.pmid: 20976106
references.citation: Biochemistry (Mosc). 2015 Feb;80(2):242-50
references.pmid: 25756539
references.citation: PLoS Genet. 2015 Jan;11(1):e1004939
references.pmid: 25617778
references.citation: J Biol Chem. 2012 Jun 15;287(25):21396-405
references.pmid: 22544743
references.citation: J Lipid Res. 2007 Dec;48(12):2531-46
references.pmid: 17872588
references.citation: Eur J Cell Biol. 2010 Feb-Mar;89(2-3):208-11
references.pmid: 19944479
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17028-33
references.pmid: 21930896
references.citation: Insect Biochem Mol Biol. 2014 Oct;53:22-9
references.pmid: 25042128
references.citation: PLoS Biol. 2004 Aug;2(8):E239
references.pmid: 15269788
references.citation: J Mol Evol. 2013 Apr;76(4):240-60
references.pmid: 23558346
references.citation: Insect Mol Biol. 2015 Feb;24(1):29-40
references.pmid: 25224926
references.citation: Infect Immun. 2001 Jun;69(6):4048-54
references.pmid: 11349075
references.citation: Dev Biol. 2014 Jan 1;385(1):23-31
references.pmid: 24183938
references.citation: Development. 2006 Jan;133(1):163-71
references.pmid: 16339194
references.citation: Arthropod Struct Dev. 2006 Sep;35(3):137-52
references.pmid: 18089066
references.citation: Clin Chem. 2009 Apr;55(4):611-22
references.pmid: 19246619
references.citation: Histochemistry. 1986;84(2):155-60
references.pmid: 3754855
references.citation: Infect Immun. 2012 Oct;80(10):3576-86
references.pmid: 22851751
references.citation: Bioinformatics. 2004 Jan 22;20(2):161-9
references.pmid: 14734306
references.citation: J Cell Sci. 2005 Feb 1;118(Pt 3):633-42
references.pmid: 15657084
references.citation: PLoS One. 2011;6(5):e19899
references.pmid: 21611131
references.citation: FEBS Lett. 2005 Dec 19;579(30):6827-33
references.pmid: 16325182
references.citation: J Biol Chem. 2015 Apr 17;290(16):10071-82
references.pmid: 25737451
references.citation: Curr Biol. 2006 Jan 24;16(2):186-94
references.pmid: 16431371
references.citation: Science. 2004 Jun 11;304(5677):1678-82
references.pmid: 15192232
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6650-5
references.pmid: 18436642
references.citation: Development. 2006 Jul;133(13):2565-74
references.pmid: 16763204
references.citation: Glycobiology. 2012 Jan;22(1):23-34
references.pmid: 21750098
references.citation: Bioessays. 2005 Oct;27(10):987-90
references.pmid: 16163734
references.citation: Insect Biochem Mol Biol. 2002 Nov;32(11):1369-82
references.pmid: 12530205
references.citation: Exp Parasitol. 2015 Apr-May;151-152:39-48
references.pmid: 25643862
references.citation: Nat Rev Immunol. 2009 Nov;9(11):799-809
references.pmid: 19855405
references.citation: Nature. 2007 Jul 12;448(7150):151-6
references.pmid: 17625558
references.citation: Dermatol Clin. 2010 Jan;28(1):93-105
references.pmid: 19945621
references.citation: J Comp Physiol B. 2006 Jan;176(1):1-15
references.pmid: 16075270
references.citation: PLoS Genet. 2015 Feb;11(2):e1004963
references.pmid: 25664770
references.citation: Int Immunol. 2015 Jun;27(6):269-80
references.pmid: 25813515
references.citation: Development. 1999 Jan;126(2):211-9
references.pmid: 9847235
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11414-9
references.pmid: 16061818