title: Endoplasmic reticulum stress triggers gametocytogenesis in the malaria parasite.
abstract: The malaria parasite experiences a significant amount of redox stress during its growth in human erythrocytes and heavily relies on secretory functions for pathogenesis. Most certainly, the parasite is equipped with machinery to tackle perturbations in the secretory pathway, like the unfolded protein response pathway in higher eukaryotes. Our bioinformatics analysis revealed the complete absence of genes involved in the canonical unfolded protein response pathway in Plasmodium falciparum. Accordingly, the parasite was unable to up-regulate endoplasmic reticulum (ER) chaperones or ER-associated degradation in response to DTT-mediated ER stress. Global profiling of gene expression upon DTT treatment revealed a network of AP2 transcription factors and their targets being activated. The overall outcome was up-regulation of genes involved in protein export and the sexual stage of the parasite life cycle culminating in gametocytogenesis. Our results suggest that the malaria parasite uses ER stress as a cue to switch to the transmissible sexual stages.
authors.affiliation: From the Department of Biochemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Chaubey
authors.affiliation: From the Department of Biochemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Grover
authors.affiliation: From the Department of Biochemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India tatu@biochem.iisc.ernet.in.
authors.forename: Utpal
authors.initials: U
authors.lastname: Tatu
mesh_terms: D059865:Endoplasmic Reticulum Stress; D005718:Gametogenesis / Q000235:genetics*; D020869:Gene Expression Profiling; D017125:Genes, Protozoan; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008018:Life Cycle Stages; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D018832:Molecular Chaperones; D015800:Protozoan Proteins; D050656:Transcription Factor AP-2
keywords: Endoplasmic Reticulum Stress (ER Stress); Gametocyte; Malaria; Microarray; Redox; Unfolded Protein Response (UPR)
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21486-91
references.pmid: 23236186
references.citation: PLoS Pathog. 2010 Oct 28;6(10):e1001165
references.pmid: 21060817
references.citation: Clin Chim Acta. 2004 Oct;348(1-2):113-20
references.pmid: 15369744
references.citation: Mol Biochem Parasitol. 2010 Sep;173(1):1-9
references.pmid: 20470832
references.citation: EMBO J. 1992 Jul;11(7):2583-93
references.pmid: 1628622
references.citation: Exp Parasitol. 2000 Mar;94(3):194-7
references.pmid: 10831385
references.citation: Mol Cell Biol. 1993 Feb;13(2):877-90
references.pmid: 8423809
references.citation: PLoS One. 2011 Apr 29;6(4):e19118
references.pmid: 21559456
references.citation: Mol Microbiol. 2007 Oct;66(2):291-302
references.pmid: 17784927
references.citation: J Biol Chem. 1999 Jun 4;274(23):16487-93
references.pmid: 10347211
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3956-61
references.pmid: 22355110
references.citation: J Biochem. 2009 Dec;146(6):743-50
references.pmid: 19861400
references.citation: J Biol Chem. 2004 Jun 18;279(25):26635-44
references.pmid: 15069061
references.citation: J Biol Chem. 1998 Dec 11;273(50):33741-9
references.pmid: 9837962
references.citation: Eur J Biochem. 1997 Dec 15;250(3):670-9
references.pmid: 9461289
references.citation: Mol Biochem Parasitol. 2011 Mar;176(1):1-7
references.pmid: 21126543
references.citation: Cell. 2000 Apr 28;101(3):249-58
references.pmid: 10847680
references.citation: Malar J. 2004 Jul 09;3:23
references.pmid: 15245577
references.citation: Biochem J. 2012 Dec 15;448(3):389-400
references.pmid: 22950671
references.citation: J Mol Biol. 2004 Jul 16;340(4):783-95
references.pmid: 15223320
references.citation: J Biol Chem. 2012 Feb 10;287(7):4403-10
references.pmid: 22147704
references.citation: Science. 2004 Dec 10;306(5703):1934-7
references.pmid: 15591203
references.citation: Malar J. 2013 Apr 15;12:129
references.pmid: 23587146
references.citation: Int J Parasitol. 2004 Feb;34(2):163-89
references.pmid: 15037104
references.citation: Int J Biochem Cell Biol. 2008;40(12):2914-26
references.pmid: 18674634
references.citation: PLoS Pathog. 2010 Apr 08;6(4):e1000853
references.pmid: 20386715
references.citation: Nucleic Acids Res. 2005 Jul 21;33(13):3994-4006
references.pmid: 16040597
references.citation: Malar J. 2004 Jul 14;3:24
references.pmid: 15253774
references.citation: Mol Cell Proteomics. 2010 Jul;9(7):1437-48
references.pmid: 20332084
references.citation: Parasitol Int. 2008 Mar;57(1):1-7
references.pmid: 17890140
references.citation: Science. 2011 Nov 25;334(6059):1081-6
references.pmid: 22116877
references.citation: Mol Microbiol. 2012 Jan;83(2):304-18
references.pmid: 22151036
references.citation: Eukaryot Cell. 2013 Jul;12(7):979-89
references.pmid: 23666622
references.citation: Cell Microbiol. 2013 Apr;15(4):647-59
references.pmid: 23114006
references.citation: Malar J. 2009 May 12;8:99
references.pmid: 19435497
references.citation: J Mol Biol. 2001 Jan 19;305(3):567-80
references.pmid: 11152613
references.citation: Mol Microbiol. 2013 May;88(4):754-71
references.pmid: 23617761
references.citation: Int J Med Microbiol. 2012 Oct;302(4-5):187-94
references.pmid: 22939033
references.citation: Science. 2006 Aug 4;313(5787):667-9
references.pmid: 16888139
references.citation: J Eukaryot Microbiol. 2005 Sep-Oct;52(5):399-451
references.pmid: 16248873
references.citation: Genome Biol. 2008;9(12):R177
references.pmid: 19091060
references.citation: Nat Rev Mol Cell Biol. 2007 Jul;8(7):519-29
references.pmid: 17565364
references.citation: Science. 2004 Dec 10;306(5703):1930-3
references.pmid: 15591202
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1701-15
references.pmid: 17941702
references.citation: Biochim Biophys Acta. 2013 Nov;1833(11):2458-63
references.pmid: 23369734
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: PLoS Pathog. 2010 Dec 23;6(12):e1001242
references.pmid: 21203490