{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:44:41Z","timestamp":1789181081591,"version":"build-2803163510"},"reference-count":81,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["P20GM134973"],"award-info":[{"award-number":["P20GM134973"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["CONFIRM grant RC05-10"],"award-info":[{"award-number":["CONFIRM grant RC05-10"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,10,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Apicomplexan parasites mobilize ionic calcium (Ca\n              <jats:sup>2+<\/jats:sup>\n              ) from intracellular stores to promote microneme secretion and facilitate motile processes including gliding motility, invasion, and egress. Recently, a multipass transmembrane protein, ICM1, was found to be\n              <jats:underline>i<\/jats:underline>\n              mportant for\n              <jats:underline>c<\/jats:underline>\n              alcium\n              <jats:underline>m<\/jats:underline>\n              obilization in\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              and\n              <jats:italic>P. berghei<\/jats:italic>\n              . Comparative genomics and phylogenetics have revealed putative ICM orthologs in\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              and other apicomplexans.\n              <jats:italic>T. gondii<\/jats:italic>\n              possesses two ICM-like proteins, which we have named TgICM1-L (TGGT1_305470) and TgICM2-L (TGGT1_309910). TgICM1-L and TgICM2-L localized to undefined puncta within the parasite cytosol. TgICM1-L and TgICM2-L are individually dispensable in tachyzoites, suggesting a potential compensatory relationship between the two proteins may exist. Surprisingly, mutants lacking both TgICM1-L and TgICM2-L are fully viable, exhibiting no obvious defects in growth, microneme secretion, invasion, or egress. Furthermore, loss of TgICM1-L, TgICM2-L, or both does not impair the parasite\u2019s ability to mobilize Ca\n              <jats:sup>2+<\/jats:sup>\n              . These findings suggest that additional proteins may participate in Ca\n              <jats:sup>2+<\/jats:sup>\n              mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in\n              <jats:italic>T. gondii<\/jats:italic>\n              . Collectively, these results highlight similar yet distinct mechanisms of Ca\n              <jats:sup>2+<\/jats:sup>\n              mobilization between\n              <jats:italic>T. gondii<\/jats:italic>\n              and\n              <jats:italic>Plasmodium<\/jats:italic>\n              .\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Ca\n                <jats:sup>2+<\/jats:sup>\n                signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca\n                <jats:sup>2+<\/jats:sup>\n                mobilization from intracellular stores in these parasites remain unclear. In\n                <jats:italic>Plasmodium<\/jats:italic>\n                , the necessity of ICM1 for Ca\n                <jats:sup>2+<\/jats:sup>\n                mobilization raises the question of whether this mechanism is conserved in other apicomplexans. Investigation into the orthologs of\n                <jats:italic>Plasmodium<\/jats:italic>\n                ICM1 in\n                <jats:italic>T. gondii<\/jats:italic>\n                revealed a differing requirement for ICM proteins between the two parasites. This study suggests that\n                <jats:italic>T. gondii<\/jats:italic>\n                employs ICM-independent mechanisms to regulate Ca\n                <jats:sup>2+<\/jats:sup>\n                homeostasis and mobilization. Proteins involved in Ca\n                <jats:sup>2+<\/jats:sup>\n                signaling in apicomplexans represent promising targets for therapeutic development.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01229-24","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T13:05:01Z","timestamp":1724159101000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Orthologs of\n            <i>Plasmodium<\/i>\n            ICM1 are dispensable for Ca\n            <sup>2+<\/sup>\n            mobilization in\n            <i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"12","author":[{"given":"Gabriel","family":"Cabral","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjian","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Bisio","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland"},{"name":"Aix-Marseille Universit\u00e9, Centre National de la Recherche Scientifique, Information G\u00e9nomique &amp; Structurale, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawson","family":"Otey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2109","authenticated-orcid":true,"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2939-1098","authenticated-orcid":true,"given":"Kevin M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49662"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.055"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00016-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2019.01.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00504-17"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8030095"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.09.007"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00518-7"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-777X.83536"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2018.07.006"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.86"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.08.003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022113155"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2012.02.007"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2017.02.007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0321-3"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2021.07.010"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9090265"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2014.12.010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007670"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2020.09.003"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14633"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14661"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001021200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02665.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvj205"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000599"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.06.069"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.10.015"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0339-8"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005491"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900402"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02694-20"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15479-3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.610408"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.05.017"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.299"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003344"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.700518"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.703546"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00375-17"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06733-w"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09022"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1210829"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006379"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000008"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004520"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.02.070"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000154"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000264"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796794"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005642"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-815041-2.00012-8"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026617666170130121042"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001806"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5396"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.019"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap7847"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007577"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv485"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1096"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3365"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198004033021404"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106154200"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2020.102337"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb501004q"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00793-21"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202553200"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.188474"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.006"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.10.6318"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.07.005"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.tb18938.x"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012354"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.09.011"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3117"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4989-y"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz991"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2728"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01229-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01229-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T13:10:31Z","timestamp":1727961031000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01229-24"}},"subtitle":[],"editor":[{"given":"Vasant","family":"Muralidharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,3]]},"references-count":81,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10,3]]}},"alternative-id":["10.1128\/spectrum.01229-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01229-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,3]]},"assertion":[{"value":"2024-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01229-24"}}