DOI: 10.1128/ec.05192-11. Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility

Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility

10.1128/ec.05192-11

Crossref journal-article

American Society for Microbiology

Eukaryotic Cell (235)

Abstract

ABSTRACT Toxoplasma gondii belongs to the phylum Apicomplexa, a group of obligate intracellular parasites that rely on gliding motility to enter host cells. Drugs interfering with the actin cytoskeleton block parasite motility, host cell invasion, and egress from infected cells. Myosin A, profilin, formin 1, formin 2, and actin-depolymerizing factor have all been implicated in parasite motility, yet little is known regarding the importance of actin polymerization and other myosins for the remaining steps of the parasite lytic cycle. Here we establish that T. gondii formin 3 (TgFRM3), a newly described formin homology 2 domain (FH2)-containing protein, binds to Toxoplasma actin and nucleates rabbit actin assembly in vitro . TgFRM3 expressed as a transgene exhibits a patchy localization at several distinct structures within the parasite. Disruption of the TgFRM3 gene by double homologous recombination in a ku80-ko strain reveals no vital function for tachyzoite propagation in vitro , which is consistent with its weak level of expression in this life stage. Conditional stabilization of truncated forms of TgFRM3 suggests that different regions of the molecule contribute to distinct localizations. Moreover, expression of TgFRM3 lacking the C-terminal domain severely affects parasite growth and replication. This work provides a first insight into how this specialized formin, restricted to the group of coccidia, completes its actin-nucleating activity.

Bibliography

Daher, W., Klages, N., Carlier, M.-F., & Soldati-Favre, D. (2012). Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility. Eukaryotic Cell, 11(3), 343â352.

Authors 4

Wassim Daher (first)
Natacha Klages (additional)
Marie-France Carlier (additional)
Dominique Soldati-Favre (additional)

References 49 Referenced 23

Dates

Type	When
Created	13 years, 8 months ago (Dec. 30, 2011, 10:28 p.m.)
Deposited	3 years, 6 months ago (Feb. 23, 2022, 6:26 a.m.)
Indexed	1 year ago (Aug. 6, 2024, 6:19 p.m.)
Issued	13 years, 6 months ago (March 1, 2012)
Published	13 years, 6 months ago (March 1, 2012)
Published Print	13 years, 6 months ago (March 1, 2012)

Funders 0

None

BibTeX

@article{Daher_2012, title={Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility}, volume={11}, ISSN={1535-9786}, url={http://dx.doi.org/10.1128/ec.05192-11}, DOI={10.1128/ec.05192-11}, number={3}, journal={Eukaryotic Cell}, publisher={American Society for Microbiology}, author={Daher, Wassim and Klages, Natacha and Carlier, Marie-France and Soldati-Favre, Dominique}, year={2012}, month=mar, pages={343–352} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        8,
        6
      ]
    ],
    "date-time": "2024-08-06T22:19:07Z",
    "timestamp": 1722982747677
  },
  "reference-count": 49,
  "publisher": "American Society for Microbiology",
  "issue": "3",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2012,
            3,
            1
          ]
        ],
        "date-time": "2012-03-01T00:00:00Z",
        "timestamp": 1330560000000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2012,
        3
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii</jats:named-content>\n            belongs to the phylum Apicomplexa, a group of obligate intracellular parasites that rely on gliding motility to enter host cells. Drugs interfering with the actin cytoskeleton block parasite motility, host cell invasion, and egress from infected cells. Myosin A, profilin, formin 1, formin 2, and actin-depolymerizing factor have all been implicated in parasite motility, yet little is known regarding the importance of actin polymerization and other myosins for the remaining steps of the parasite lytic cycle. Here we establish that\n            <jats:named-content content-type=\"genus-species\">T. gondii</jats:named-content>\n            formin 3 (TgFRM3), a newly described formin homology 2 domain (FH2)-containing protein, binds to\n            <jats:named-content content-type=\"genus-species\">Toxoplasma</jats:named-content>\n            actin and nucleates rabbit actin assembly\n            <jats:italic>in vitro</jats:italic>\n            . TgFRM3 expressed as a transgene exhibits a patchy localization at several distinct structures within the parasite. Disruption of the\n            <jats:italic>TgFRM3</jats:italic>\n            gene by double homologous recombination in a\n            <jats:italic>ku80-ko</jats:italic>\n            strain reveals no vital function for tachyzoite propagation\n            <jats:italic>in vitro</jats:italic>\n            , which is consistent with its weak level of expression in this life stage. Conditional stabilization of truncated forms of TgFRM3 suggests that different regions of the molecule contribute to distinct localizations. Moreover, expression of TgFRM3 lacking the C-terminal domain severely affects parasite growth and replication. This work provides a first insight into how this specialized formin, restricted to the group of coccidia, completes its actin-nucleating activity.\n          </jats:p>",
  "DOI": "10.1128/ec.05192-11",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2011,
        12,
        31
      ]
    ],
    "date-time": "2011-12-31T03:28:54Z",
    "timestamp": 1325302134000
  },
  "page": "343-352",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 23,
  "title": "Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility",
  "prefix": "10.1128",
  "volume": "11",
  "author": [
    {
      "given": "Wassim",
      "family": "Daher",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland"
        }
      ]
    },
    {
      "given": "Natacha",
      "family": "Klages",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland"
        }
      ]
    },
    {
      "given": "Marie-France",
      "family": "Carlier",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales UPR A 9063, CNRS, Gif sur Yvette, France"
        }
      ]
    },
    {
      "given": "Dominique",
      "family": "Soldati-Favre",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M006205200"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M109.093914"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrmicro1465"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.chom.2008.02.006"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1001094"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/mcp.M110.000745"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1001132"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.mib.2009.06.008"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200012116"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81071-5"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.24.14010"
    },
    {
      "key": "e_1_3_3_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.24.11703"
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0506307103"
    },
    {
      "key": "e_1_3_3_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/EC.00357-08"
    },
    {
      "key": "e_1_3_3_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.0030077"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.75.103004.142647"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/EC.00064-08"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/1471-2164-6-179"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.02949"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1000754"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nmeth1134"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/21.9.2149"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.tibs.2005.04.014"
    },
    {
      "key": "e_1_3_3_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.0020013"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/EC.00358-08"
    },
    {
      "key": "e_1_3_3_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200211078"
    },
    {
      "key": "e_1_3_3_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.pone.0012302"
    },
    {
      "key": "e_1_3_3_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e10-12-0939"
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.115.3.563"
    },
    {
      "key": "e_1_3_3_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.02762"
    },
    {
      "key": "e_1_3_3_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0076-6879(06)06016-2"
    },
    {
      "key": "e_1_3_3_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.021089"
    },
    {
      "key": "e_1_3_3_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/cm.20379"
    },
    {
      "key": "e_1_3_3_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.chom.2008.01.001"
    },
    {
      "key": "e_1_3_3_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.ceb.2009.11.010"
    },
    {
      "key": "e_1_3_3_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e05-06-0512"
    },
    {
      "key": "e_1_3_3_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.jmb.2005.03.056"
    },
    {
      "key": "e_1_3_3_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.bbamcr.2010.01.014"
    },
    {
      "key": "e_1_3_3_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1600-0854.2006.00484.x"
    },
    {
      "key": "e_1_3_3_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.febslet.2004.12.037"
    },
    {
      "key": "e_1_3_3_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.113.7.1241"
    },
    {
      "key": "e_1_3_3_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.copbio.2010.05.009"
    },
    {
      "key": "e_1_3_3_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.1002280"
    },
    {
      "key": "e_1_3_3_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.ppat.0030078"
    },
    {
      "key": "e_1_3_3_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.molbiopara.2011.09.006"
    },
    {
      "key": "e_1_3_3_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/emboj.2008.7"
    },
    {
      "key": "e_1_3_3_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.chom.2011.09.004"
    },
    {
      "key": "e_1_3_3_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1600-0854.2009.00893.x"
    },
    {
      "key": "e_1_3_3_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e02-08-0458"
    }
  ],
  "container-title": "Eukaryotic Cell",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/EC.05192-11",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/EC.05192-11",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        2,
        23
      ]
    ],
    "date-time": "2022-02-23T11:26:46Z",
    "timestamp": 1645615606000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/EC.05192-11"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2012,
        3
      ]
    ]
  },
  "references-count": 49,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2012,
          3
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/EC.05192-11"
  ],
  "URL": "http://dx.doi.org/10.1128/EC.05192-11",
  "relation": {},
  "ISSN": [
    "1535-9778",
    "1535-9786"
  ],
  "subject": [],
  "container-title-short": "Eukaryot Cell",
  "published": {
    "date-parts": [
      [
        2012,
        3
      ]
    ]
  },
  "assertion": [
    {
      "value": "2011-07-29",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2011-12-19",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2012-02-28",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}