Analysis of Ca 2 + mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules
Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca signaling although the temporal dynamics of Ca fluxes and down-stream second messenger pathway...
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Published in | Cellular microbiology Vol. 19; no. 4 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
01.04.2017
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Abstract | Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca
signaling although the temporal dynamics of Ca
fluxes and down-stream second messenger pathways are poorly understood. Here, we use a genetically encoded biosensor, GFP-Calmodulin-M13-6 (GCaMP6), to capture Ca
flux in live Toxoplasma and investigate the role of Ca
signaling in egress and motility. Our analysis determines how environmental cues and signal activation influence intracellular Ca
flux, allowing placement of effector molecules within this pathway. Importantly, we have identified key interrelationships between cGMP and Ca
signaling that are required for activation of egress and motility. Furthermore, we extend this analysis to show that the Ca
Dependent Protein Kinases-TgCDPK1 and TgCDPK3-play a role in signal quenching before egress. This work highlights the interrelationships of second messenger pathways of Toxoplasma in space and time, which is likely required for pathogenesis of all apicomplexan species. |
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AbstractList | Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca
signaling although the temporal dynamics of Ca
fluxes and down-stream second messenger pathways are poorly understood. Here, we use a genetically encoded biosensor, GFP-Calmodulin-M13-6 (GCaMP6), to capture Ca
flux in live Toxoplasma and investigate the role of Ca
signaling in egress and motility. Our analysis determines how environmental cues and signal activation influence intracellular Ca
flux, allowing placement of effector molecules within this pathway. Importantly, we have identified key interrelationships between cGMP and Ca
signaling that are required for activation of egress and motility. Furthermore, we extend this analysis to show that the Ca
Dependent Protein Kinases-TgCDPK1 and TgCDPK3-play a role in signal quenching before egress. This work highlights the interrelationships of second messenger pathways of Toxoplasma in space and time, which is likely required for pathogenesis of all apicomplexan species. |
Author | Tonkin, Christopher J Whitehead, Lachlan Lessene, Guillaume Nijagal, Brunda Rogers, Kelly L Stewart, Rebecca J Sleebs, Brad E McConville, Malcolm J |
Author_xml | – sequence: 1 givenname: Rebecca J surname: Stewart fullname: Stewart, Rebecca J organization: Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia – sequence: 2 givenname: Lachlan surname: Whitehead fullname: Whitehead, Lachlan organization: Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia – sequence: 3 givenname: Brunda surname: Nijagal fullname: Nijagal, Brunda organization: Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia – sequence: 4 givenname: Brad E surname: Sleebs fullname: Sleebs, Brad E organization: Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia – sequence: 5 givenname: Guillaume surname: Lessene fullname: Lessene, Guillaume organization: Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria, Australia – sequence: 6 givenname: Malcolm J surname: McConville fullname: McConville, Malcolm J organization: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia – sequence: 7 givenname: Kelly L surname: Rogers fullname: Rogers, Kelly L organization: Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia – sequence: 8 givenname: Christopher J surname: Tonkin fullname: Tonkin, Christopher J organization: Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27781359$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1111/j.1365-2958.2004.04464.x 10.1016/j.chom.2009.11.007 10.1016/j.ijpara.2005.08.014 10.1371/journal.ppat.1003049 10.1016/j.chom.2016.02.006 10.1038/nsmb.1795 10.1126/science.1188191 10.1371/journal.ppat.1004488 10.1016/j.chom.2009.05.017 10.1126/science.1165740 10.1016/S0166-6851(01)00451-0 10.1038/nature09022 10.1242/jcs.00596 10.1016/j.ceca.2014.12.010 10.1038/nrm1155 10.1371/journal.pbio.1001806 10.1128/IAI.00416-13 10.4049/jimmunol.179.12.8357 10.1042/BJ20041971 10.1074/jbc.M112.411934 10.1242/jcs.01495 10.1128/MCB.20.24.9399-9408.2000 10.1016/j.molbiopara.2006.05.003 10.1111/cmi.12289 10.1016/j.bmcl.2005.04.060 10.1074/jbc.M115.700518 10.1038/nature12354 10.1016/j.bmcl.2013.03.036 10.1016/j.chom.2012.05.014 10.1016/S0092-8674(04)00449-0 10.1182/blood-2015-09-666834 10.1038/emboj.2012.299 10.1128/mBio.00845-15 10.1128/EC.00262-07 10.1046/j.1365-2958.1999.01174.x 10.1021/cb501004q 10.1074/jbc.M115.652511 10.1016/j.bbrc.2010.02.117 10.1016/j.bbamcr.2008.10.005 10.1074/jbc.M106154200 10.1016/j.ijpara.2009.04.003 10.1016/j.ijpara.2003.11.019 10.1371/journal.ppat.1003344 10.1111/j.1365-2958.2008.06267.x 10.1074/jbc.M202553200 10.1074/jbc.M115.703546 10.1371/journal.ppat.1003066 10.1016/j.semcdb.2015.09.020 10.1038/nature06478 |
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References | e_1_2_7_5_1 e_1_2_7_3_1 e_1_2_7_9_1 e_1_2_7_7_1 e_1_2_7_19_1 e_1_2_7_17_1 e_1_2_7_15_1 e_1_2_7_41_1 e_1_2_7_13_1 e_1_2_7_43_1 e_1_2_7_11_1 e_1_2_7_45_1 e_1_2_7_47_1 e_1_2_7_26_1 e_1_2_7_49_1 e_1_2_7_28_1 e_1_2_7_50_1 e_1_2_7_25_1 e_1_2_7_31_1 e_1_2_7_52_1 Carruthers V. B. (e_1_2_7_14_1) 1997; 73 e_1_2_7_23_1 e_1_2_7_33_1 e_1_2_7_21_1 e_1_2_7_35_1 e_1_2_7_37_1 e_1_2_7_39_1 e_1_2_7_6_1 e_1_2_7_4_1 e_1_2_7_8_1 e_1_2_7_18_1 e_1_2_7_16_1 e_1_2_7_40_1 e_1_2_7_2_1 e_1_2_7_42_1 e_1_2_7_12_1 e_1_2_7_44_1 e_1_2_7_10_1 e_1_2_7_46_1 e_1_2_7_48_1 e_1_2_7_27_1 e_1_2_7_29_1 e_1_2_7_51_1 e_1_2_7_30_1 e_1_2_7_24_1 e_1_2_7_32_1 e_1_2_7_22_1 e_1_2_7_34_1 e_1_2_7_20_1 e_1_2_7_36_1 e_1_2_7_38_1 |
References_xml | – ident: e_1_2_7_33_1 doi: 10.1111/j.1365-2958.2004.04464.x – ident: e_1_2_7_36_1 doi: 10.1016/j.chom.2009.11.007 – ident: e_1_2_7_22_1 doi: 10.1016/j.ijpara.2005.08.014 – ident: e_1_2_7_23_1 doi: 10.1371/journal.ppat.1003049 – ident: e_1_2_7_12_1 doi: 10.1016/j.chom.2016.02.006 – ident: e_1_2_7_48_1 doi: 10.1038/nsmb.1795 – ident: e_1_2_7_21_1 doi: 10.1126/science.1188191 – ident: e_1_2_7_42_1 doi: 10.1371/journal.ppat.1004488 – ident: e_1_2_7_7_1 doi: 10.1016/j.chom.2009.05.017 – ident: e_1_2_7_27_1 doi: 10.1126/science.1165740 – ident: e_1_2_7_19_1 doi: 10.1016/S0166-6851(01)00451-0 – ident: e_1_2_7_52_1 – ident: e_1_2_7_29_1 doi: 10.1038/nature09022 – ident: e_1_2_7_31_1 doi: 10.1242/jcs.00596 – ident: e_1_2_7_28_1 doi: 10.1016/j.ceca.2014.12.010 – ident: e_1_2_7_4_1 doi: 10.1038/nrm1155 – ident: e_1_2_7_10_1 doi: 10.1371/journal.pbio.1001806 – ident: e_1_2_7_39_1 doi: 10.1128/IAI.00416-13 – ident: e_1_2_7_41_1 doi: 10.4049/jimmunol.179.12.8357 – ident: e_1_2_7_17_1 doi: 10.1042/BJ20041971 – ident: e_1_2_7_2_1 doi: 10.1074/jbc.M112.411934 – ident: e_1_2_7_49_1 doi: 10.1242/jcs.01495 – ident: e_1_2_7_8_1 doi: 10.1128/MCB.20.24.9399-9408.2000 – ident: e_1_2_7_20_1 doi: 10.1016/j.molbiopara.2006.05.003 – ident: e_1_2_7_13_1 doi: 10.1111/cmi.12289 – ident: e_1_2_7_5_1 doi: 10.1016/j.bmcl.2005.04.060 – ident: e_1_2_7_11_1 doi: 10.1074/jbc.M115.700518 – ident: e_1_2_7_16_1 doi: 10.1038/nature12354 – ident: e_1_2_7_46_1 doi: 10.1016/j.bmcl.2013.03.036 – ident: e_1_2_7_43_1 doi: 10.1016/j.chom.2012.05.014 – ident: e_1_2_7_6_1 doi: 10.1016/S0092-8674(04)00449-0 – ident: e_1_2_7_25_1 doi: 10.1182/blood-2015-09-666834 – ident: e_1_2_7_30_1 doi: 10.1038/emboj.2012.299 – ident: e_1_2_7_51_1 doi: 10.1128/mBio.00845-15 – ident: e_1_2_7_37_1 doi: 10.1128/EC.00262-07 – ident: e_1_2_7_15_1 doi: 10.1046/j.1365-2958.1999.01174.x – ident: e_1_2_7_26_1 doi: 10.1021/cb501004q – ident: e_1_2_7_9_1 doi: 10.1074/jbc.M115.652511 – ident: e_1_2_7_47_1 doi: 10.1016/j.bbrc.2010.02.117 – ident: e_1_2_7_3_1 doi: 10.1016/j.bbamcr.2008.10.005 – ident: e_1_2_7_35_1 doi: 10.1074/jbc.M106154200 – ident: e_1_2_7_40_1 doi: 10.1016/j.ijpara.2009.04.003 – volume: 73 start-page: 114 year: 1997 ident: e_1_2_7_14_1 article-title: Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts publication-title: European Journal of Cell Biology contributor: fullname: Carruthers V. B. – ident: e_1_2_7_50_1 doi: 10.1016/j.ijpara.2003.11.019 – ident: e_1_2_7_18_1 doi: 10.1371/journal.ppat.1003344 – ident: e_1_2_7_45_1 doi: 10.1111/j.1365-2958.2008.06267.x – ident: e_1_2_7_32_1 doi: 10.1074/jbc.M202553200 – ident: e_1_2_7_44_1 doi: 10.1074/jbc.M115.703546 – ident: e_1_2_7_34_1 doi: 10.1371/journal.ppat.1003066 – ident: e_1_2_7_24_1 doi: 10.1016/j.semcdb.2015.09.020 – ident: e_1_2_7_38_1 doi: 10.1038/nature06478 |
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SubjectTerms | Calcium Signaling Cells, Cultured Cyclic GMP - metabolism Cyclic GMP-Dependent Protein Kinases - metabolism Host-Parasite Interactions Humans Toxoplasma - pathogenicity Toxoplasma - physiology Toxoplasmosis - parasitology |
Title | Analysis of Ca 2 + mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules |
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