Dauer signalling pathway model for Haemonchus contortus.
Dauer signalling pathway
Haemonchus contortus
Phospho-proteomic analysis
Proteomic analysis
Transcriptomic analysis
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
29 Apr 2019
29 Apr 2019
Historique:
received:
24
01
2019
accepted:
28
03
2019
entrez:
1
5
2019
pubmed:
1
5
2019
medline:
31
5
2019
Statut:
epublish
Résumé
Signalling pathways have been extensively investigated in the free-living nematode Caenorhabditis elegans, but very little is known about these pathways in parasitic nematodes. Here, we constructed a model for the dauer-associated signalling pathways in an economically highly significant parasitic worm, Haemonchus contortus. Guided by data and information available for C. elegans, we used extensive genomic and transcriptomic datasets to infer gene homologues in the dauer-associated pathways, explore developmental transcriptomic, proteomic and phosphoproteomic profiles in H. contortus and study selected molecular structures. The canonical cyclic guanosine monophosphate (cGMP), transforming growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and steroid hormone signalling pathways of H. contortus were inferred to represent a total of 61 gene homologues. Compared with C. elegans, H. contortus has a reduced set of genes encoding insulin-like peptides, implying evolutionary and biological divergences between the parasitic and free-living nematodes. Similar transcription profiles were found for all gene homologues between the infective stage of H. contortus and dauer stage of C. elegans. High transcriptional levels for genes encoding G protein-coupled receptors (GPCRs), TGF-β, insulin-like ligands (e.g. ins-1, ins-17 and ins-18) and transcriptional factors (e.g. daf-16) in the infective L3 stage of H. contortus were suggestive of critical functional roles in this stage. Conspicuous protein expression patterns and extensive phosphorylation of some components of these pathways suggested marked post-translational modifications also in the L3 stage. The high structural similarity in the DAF-12 ligand binding domain among nematodes indicated functional conservation in steroid (i.e. dafachronic acid) signalling linked to worm development. Taken together, this pathway model provides a basis to explore hypotheses regarding biological processes and regulatory mechanisms (via particular microRNAs, phosphorylation events and/or lipids) associated with the development of H. contortus and related nematodes as well as parasite-host cross talk, which could aid the discovery of new therapeutic targets.
Sections du résumé
BACKGROUND
BACKGROUND
Signalling pathways have been extensively investigated in the free-living nematode Caenorhabditis elegans, but very little is known about these pathways in parasitic nematodes. Here, we constructed a model for the dauer-associated signalling pathways in an economically highly significant parasitic worm, Haemonchus contortus.
METHODS
METHODS
Guided by data and information available for C. elegans, we used extensive genomic and transcriptomic datasets to infer gene homologues in the dauer-associated pathways, explore developmental transcriptomic, proteomic and phosphoproteomic profiles in H. contortus and study selected molecular structures.
RESULTS
RESULTS
The canonical cyclic guanosine monophosphate (cGMP), transforming growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and steroid hormone signalling pathways of H. contortus were inferred to represent a total of 61 gene homologues. Compared with C. elegans, H. contortus has a reduced set of genes encoding insulin-like peptides, implying evolutionary and biological divergences between the parasitic and free-living nematodes. Similar transcription profiles were found for all gene homologues between the infective stage of H. contortus and dauer stage of C. elegans. High transcriptional levels for genes encoding G protein-coupled receptors (GPCRs), TGF-β, insulin-like ligands (e.g. ins-1, ins-17 and ins-18) and transcriptional factors (e.g. daf-16) in the infective L3 stage of H. contortus were suggestive of critical functional roles in this stage. Conspicuous protein expression patterns and extensive phosphorylation of some components of these pathways suggested marked post-translational modifications also in the L3 stage. The high structural similarity in the DAF-12 ligand binding domain among nematodes indicated functional conservation in steroid (i.e. dafachronic acid) signalling linked to worm development.
CONCLUSIONS
CONCLUSIONS
Taken together, this pathway model provides a basis to explore hypotheses regarding biological processes and regulatory mechanisms (via particular microRNAs, phosphorylation events and/or lipids) associated with the development of H. contortus and related nematodes as well as parasite-host cross talk, which could aid the discovery of new therapeutic targets.
Identifiants
pubmed: 31036054
doi: 10.1186/s13071-019-3419-6
pii: 10.1186/s13071-019-3419-6
pmc: PMC6489264
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
187Subventions
Organisme : National Health and Medical Research Council
ID : CDF1
Références
WormBook. 2007 Aug 08;:1-19
pubmed: 17988074
Parasitol Res. 2012 Jan;110(1):151-9
pubmed: 21607689
Int J Parasitol. 2009 Aug;39(10):1071-81
pubmed: 19401205
WormBook. 2015 Jun 18;:1-31
pubmed: 26087236
Int J Parasitol. 2007 Feb;37(2):221-31
pubmed: 17112525
Vet Parasitol. 2009 Feb 5;159(2):139-48
pubmed: 19054616
FASEB J. 2017 Oct;31(10):4515-4532
pubmed: 28687609
Exp Parasitol. 2011 Aug;128(4):309-17
pubmed: 21510934
WormBook. 2006 Jun 14;:1-19
pubmed: 18050452
Int J Parasitol. 2014 Jun;44(7):485-96
pubmed: 24727120
Parasit Vectors. 2016 Jul 29;9(1):422
pubmed: 27472920
Cell. 2006 Mar 24;124(6):1209-23
pubmed: 16529801
Adv Parasitol. 2016;93:353-96
pubmed: 27238008
Biosci Biotechnol Biochem. 2012;76(11):2168-72
pubmed: 23132577
Folia Parasitol (Praha). 2000;47(2):135-40
pubmed: 10945738
Parasit Vectors. 2016 Feb 03;9:65
pubmed: 26842781
WormBook. 2006 Oct 25;:1-29
pubmed: 18050433
Nucleic Acids Res. 2002 Jul 15;30(14):3059-66
pubmed: 12136088
Sci Rep. 2018 May 1;8(1):6808
pubmed: 29717207
J Clin Invest. 2017 Apr 3;127(4):1165-1171
pubmed: 28165341
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Parasitol Today. 1993 Jan;9(1):23-6
pubmed: 15463660
WormBook. 2013 Dec 26;:1-43
pubmed: 24395814
Parasitology. 2006 Mar;132(Pt 3):403-9
pubmed: 16332287
Bioinformatics. 2014 May 1;30(9):1236-40
pubmed: 24451626
BMC Bioinformatics. 2005 Feb 15;6:31
pubmed: 15713233
Genes Dev. 2000 Jun 15;14(12):1512-27
pubmed: 10859169
Cell. 2005 Feb 25;120(4):449-60
pubmed: 15734678
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Genome Biol Evol. 2018 Feb 1;10(2):396-409
pubmed: 29267942
PLoS Pathog. 2014 Jul 10;10(7):e1004235
pubmed: 25010340
Science. 2009 Apr 3;324(5923):95-8
pubmed: 19342589
Parasit Vectors. 2016 Feb 03;9:64
pubmed: 26842675
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18668-73
pubmed: 19828440
Development. 2004 Apr;131(8):1765-76
pubmed: 15084461
Int J Parasitol. 2014 Oct 1;44(11):775-86
pubmed: 25058511
Genome Biol. 2013 Aug 28;14(8):R89
pubmed: 23985341
Genome Biol. 2013 Aug 28;14(8):R88
pubmed: 23985316
Adv Parasitol. 1986;25:129-74
pubmed: 3535434
Int J Parasitol. 1995 May;25(5):561-8
pubmed: 7635634
Int J Parasitol. 2014 Jan;44(1):1-8
pubmed: 24095839
Genes Dev. 2008 Aug 15;22(16):2149-65
pubmed: 18708575
Biochem Biophys Res Commun. 2012 Jul 6;423(3):478-83
pubmed: 22683638
PLoS Pathog. 2016 Jan 04;12(1):e1005358
pubmed: 26727267
Bioessays. 2018 Feb;40(2):
pubmed: 29280502
Int J Parasitol. 2006 Jul;36(8):859-68
pubmed: 16759659
Parasitology. 2010 Jan;137(1):159-71
pubmed: 19712539
Nature. 2010 Jul 22;466(7305):494-7
pubmed: 20592728
Mol Cell Proteomics. 2012 Dec;11(12):1631-9
pubmed: 22923814
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Genome Biol Evol. 2013;5(7):1246-60
pubmed: 23729632
Gene. 2002 Jan 9;282(1-2):33-41
pubmed: 11814675
Genes Dev. 2003 Apr 1;17(7):844-58
pubmed: 12654727
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9138-43
pubmed: 19497877
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):460-5
pubmed: 10618440
Cell. 2009 Jan 23;136(2):215-33
pubmed: 19167326
Adv Parasitol. 2016;93:569-98
pubmed: 27238013
Genes Dev. 2001 Mar 15;15(6):672-86
pubmed: 11274053
Int J Parasitol. 2018 Aug;48(9-10):763-772
pubmed: 29792880
Nat Rev Genet. 2008 Feb;9(2):102-14
pubmed: 18197166
Cell. 2017 Apr 20;169(3):381-405
pubmed: 28431241
Genome Res. 2002 Apr;12(4):656-64
pubmed: 11932250
Int J Parasitol. 2010 Mar 15;40(4):405-15
pubmed: 19796644
PLoS Genet. 2015 Mar 16;11(3):e1005027
pubmed: 25774872
Nat Chem Biol. 2017 May 17;13(6):577-586
pubmed: 28514418
Parasit Vectors. 2014 Nov 12;7:498
pubmed: 25388625
PLoS Biol. 2012;10(4):e1001307
pubmed: 22505849
Parasit Vectors. 2019 Jan 14;12(1):32
pubmed: 30642380
Bioinformatics. 1998;14(4):380-1
pubmed: 9632837
Bioinformatics. 2001 Sep;17(9):847-8
pubmed: 11590104
Nat Struct Mol Biol. 2018 Jan;25(1):4-12
pubmed: 29323277
Int J Parasitol. 2002 Apr;32(4):399-404
pubmed: 11849636
Genome Biol. 2007;8(10):R211
pubmed: 17919324
PLoS Negl Trop Dis. 2012;6(10):e1854
pubmed: 23145190
WormBook. 2013 Jul 10;:1-34
pubmed: 23908056
Curr Clin Microbiol Rep. 2016 Dec;3(4):186-197
pubmed: 28781934
Adv Parasitol. 2016;93:95-143
pubmed: 27238004
Genome Res. 1999 Sep;9(9):868-77
pubmed: 10508846
BMC Genomics. 2012 Jan 04;13:4
pubmed: 22216965
Nucleic Acids Res. 2018 Jan 4;46(D1):D869-D874
pubmed: 29069413
Curr Biol. 2009 Jan 13;19(1):67-71
pubmed: 19110431
Int J Parasitol. 2005 Dec;35(14):1473-5
pubmed: 16139836
PLoS Genet. 2011 Jul;7(7):e1002179
pubmed: 21814518
Parasitol Res. 2007 Sep;101(4):1111-5
pubmed: 17558520
Nat Struct Mol Biol. 2010 Jun;17(6):666-72
pubmed: 20495563
Int J Parasitol. 2003 Jul 30;33(8):787-93
pubmed: 12865078
J Proteome Res. 2009 Aug;8(8):4039-49
pubmed: 19530675
WormBook. 2015 Jun 09;:1-49
pubmed: 26069085
BMC Genomics. 2016 Jun 27;17:476
pubmed: 27350342
Biotechnol Adv. 2016 Sep-Oct;34(5):663-686
pubmed: 26956711
Curr Opin Cell Biol. 2018 Apr;51:42-49
pubmed: 29153704
Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):204-209
pubmed: 29203662
Science. 2005 Dec 23;310(5756):1954-7
pubmed: 16373574
PLoS Genet. 2017 Nov 2;13(11):e1007046
pubmed: 29095825