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The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence

Identifieur interne : 001594 ( Main/Exploration ); précédent : 001593; suivant : 001595

The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence

Auteurs : Laurence Berry [France] ; Chun-Ti Chen [États-Unis] ; Luc Reininger [France] ; Teresa G. Carvalho ; Hiba El Hajj [Liban] ; Juliette Morlon-Guyot [France] ; Yann Bordat [France] ; Maryse Lebrun [France] ; Marc-Jan Gubbels [États-Unis] ; Christian Doerig ; Wassim Daher [France]

Source :

RBID : PMC:4961599

Descripteurs français

English descriptors

Abstract

Aurora kinases are eukaryotic serine/threonine protein kinases that regulate key events associated with chromatin condensation, centrosome and spindle function, and cytokinesis. Elucidating the roles of Aurora kinases in apicomplexan parasites is crucial to understand the cell cycle control during Plasmodium schizogony or Toxoplasma endodyogeny. Here, we report on the localization of two previously uncharacterized Toxoplasma Aurora-related kinases (Ark2 and Ark3) in tachyzoites and of the uncharacterized Ark3 orthologue in Plasmodium falciparum erythrocytic stages. In T. gondii, we show that TgArk2 and TgArk3 concentrate at specific sub-cellular structures linked to parasite division: the mitotic spindle and intranuclear mitotic structures (TgArk2), and the outer core of the centrosome and the budding daughter cells cytoskeleton (TgArk3). By tagging the endogenous PfArk3 gene with the green fluorescent protein (GFP) in live parasites, we show that PfArk3 protein expression peaks late in schizogony and localizes at the periphery of budding schizonts. Disruption of the TgArk2 gene reveals no essential function for tachyzoite propagation in vitro, which is surprising giving that the P. falciparum and P. berghei orthologues are essential for erythrocyte schizogony. In contrast, knock-down of TgArk3 protein results in pronounced defects in parasite division and a major growth deficiency. TgArk3-depleted parasites display several defects, such as reduced parasite growth rate, delayed egress and parasite duplication, defect in rosette formation, reduced parasite size and invasion efficiency and lack of virulence in mice. Our study provides new insights into cell cycle control in Toxoplasma and malaria parasites, and highlights Aurora kinase 3 as potential drug target.


Url:
DOI: 10.1111/cmi.12571
PubMed: 26833682
PubMed Central: 4961599


Affiliations:


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Le document en format XML

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<name sortKey="Carvalho, Teresa G" sort="Carvalho, Teresa G" uniqKey="Carvalho T" first="Teresa G." last="Carvalho">Teresa G. Carvalho</name>
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<name sortKey="Bordat, Yann" sort="Bordat, Yann" uniqKey="Bordat Y" first="Yann" last="Bordat">Yann Bordat</name>
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<name sortKey="Lebrun, Maryse" sort="Lebrun, Maryse" uniqKey="Lebrun M" first="Maryse" last="Lebrun">Maryse Lebrun</name>
<affiliation wicri:level="3">
<nlm:aff id="A1">Dynamique des Interactions Membranaires Normales et Pathologiques, UMR5235 CNRS, Université Montpellier, Montpellier, France</nlm:aff>
<country xml:lang="fr">France</country>
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<name sortKey="Doerig, Christian" sort="Doerig, Christian" uniqKey="Doerig C" first="Christian" last="Doerig">Christian Doerig</name>
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<wicri:noCountry code="subfield">3800</wicri:noCountry>
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<title level="j">Cellular microbiology</title>
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<idno type="eISSN">1462-5822</idno>
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<date when="2016">2016</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Aurora Kinases (physiology)</term>
<term>Female</term>
<term>Host-Parasite Interactions</term>
<term>Mice</term>
<term>Protein Transport</term>
<term>Protozoan Proteins (physiology)</term>
<term>Toxoplasma (enzymology)</term>
<term>Toxoplasma (physiology)</term>
<term>Toxoplasma (ultrastructure)</term>
<term>Toxoplasmosis (parasitology)</term>
<term>Virulence</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Aurora kinases (physiologie)</term>
<term>Femelle</term>
<term>Interactions hôte-parasite</term>
<term>Protéines de protozoaire (physiologie)</term>
<term>Souris</term>
<term>Toxoplasma (enzymologie)</term>
<term>Toxoplasma (physiologie)</term>
<term>Toxoplasma (ultrastructure)</term>
<term>Toxoplasmose (parasitologie)</term>
<term>Transport de protéines</term>
<term>Virulence</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en">
<term>Aurora Kinases</term>
<term>Protozoan Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr">
<term>Toxoplasma</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>Toxoplasma</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr">
<term>Toxoplasmose</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitology" xml:lang="en">
<term>Toxoplasmosis</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Aurora kinases</term>
<term>Protéines de protozoaire</term>
<term>Toxoplasma</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Toxoplasma</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en">
<term>Toxoplasma</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Female</term>
<term>Host-Parasite Interactions</term>
<term>Mice</term>
<term>Protein Transport</term>
<term>Virulence</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="fr">
<term>Animaux</term>
<term>Femelle</term>
<term>Interactions hôte-parasite</term>
<term>Souris</term>
<term>Toxoplasma</term>
<term>Transport de protéines</term>
<term>Virulence</term>
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<front>
<div type="abstract" xml:lang="en">
<p id="P1">Aurora kinases are eukaryotic serine/threonine protein kinases that regulate key events associated with chromatin condensation, centrosome and spindle function, and cytokinesis. Elucidating the roles of Aurora kinases in apicomplexan parasites is crucial to understand the cell cycle control during
<italic>Plasmodium</italic>
schizogony or
<italic>Toxoplasma</italic>
endodyogeny. Here, we report on the localization of two previously uncharacterized
<italic>Toxoplasma</italic>
Aurora-related kinases (Ark2 and Ark3) in tachyzoites and of the uncharacterized Ark3 orthologue in
<italic>Plasmodium falciparum</italic>
erythrocytic stages. In
<italic>T. gondii</italic>
, we show that TgArk2 and TgArk3 concentrate at specific sub-cellular structures linked to parasite division: the mitotic spindle and intranuclear mitotic structures (TgArk2), and the outer core of the centrosome and the budding daughter cells cytoskeleton (TgArk3). By tagging the endogenous
<italic>PfArk3</italic>
gene with the green fluorescent protein (GFP) in live parasites, we show that PfArk3 protein expression peaks late in schizogony and localizes at the periphery of budding schizonts. Disruption of the
<italic>TgArk2</italic>
gene reveals no essential function for tachyzoite propagation
<italic>in vitro</italic>
, which is surprising giving that the
<italic>P. falciparum</italic>
and
<italic>P. berghei</italic>
orthologues are essential for erythrocyte schizogony. In contrast, knock-down of TgArk3 protein results in pronounced defects in parasite division and a major growth deficiency. TgArk3-depleted parasites display several defects, such as reduced parasite growth rate, delayed egress and parasite duplication, defect in rosette formation, reduced parasite size and invasion efficiency and lack of virulence in mice. Our study provides new insights into cell cycle control in
<italic>Toxoplasma</italic>
and malaria parasites, and highlights Aurora kinase 3 as potential drug target.</p>
</div>
</front>
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<affiliations>
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<country>
<li>France</li>
<li>Liban</li>
<li>États-Unis</li>
</country>
<region>
<li>Languedoc-Roussillon</li>
<li>Massachusetts</li>
<li>Occitanie (région administrative)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Montpellier</li>
<li>Paris</li>
</settlement>
</list>
<tree>
<noCountry>
<name sortKey="Carvalho, Teresa G" sort="Carvalho, Teresa G" uniqKey="Carvalho T" first="Teresa G." last="Carvalho">Teresa G. Carvalho</name>
<name sortKey="Doerig, Christian" sort="Doerig, Christian" uniqKey="Doerig C" first="Christian" last="Doerig">Christian Doerig</name>
</noCountry>
<country name="France">
<region name="Occitanie (région administrative)">
<name sortKey="Berry, Laurence" sort="Berry, Laurence" uniqKey="Berry L" first="Laurence" last="Berry">Laurence Berry</name>
</region>
<name sortKey="Bordat, Yann" sort="Bordat, Yann" uniqKey="Bordat Y" first="Yann" last="Bordat">Yann Bordat</name>
<name sortKey="Daher, Wassim" sort="Daher, Wassim" uniqKey="Daher W" first="Wassim" last="Daher">Wassim Daher</name>
<name sortKey="Lebrun, Maryse" sort="Lebrun, Maryse" uniqKey="Lebrun M" first="Maryse" last="Lebrun">Maryse Lebrun</name>
<name sortKey="Morlon Guyot, Juliette" sort="Morlon Guyot, Juliette" uniqKey="Morlon Guyot J" first="Juliette" last="Morlon-Guyot">Juliette Morlon-Guyot</name>
<name sortKey="Reininger, Luc" sort="Reininger, Luc" uniqKey="Reininger L" first="Luc" last="Reininger">Luc Reininger</name>
</country>
<country name="États-Unis">
<region name="Massachusetts">
<name sortKey="Chen, Chun Ti" sort="Chen, Chun Ti" uniqKey="Chen C" first="Chun-Ti" last="Chen">Chun-Ti Chen</name>
</region>
<name sortKey="Gubbels, Marc Jan" sort="Gubbels, Marc Jan" uniqKey="Gubbels M" first="Marc-Jan" last="Gubbels">Marc-Jan Gubbels</name>
</country>
<country name="Liban">
<noRegion>
<name sortKey="El Hajj, Hiba" sort="El Hajj, Hiba" uniqKey="El Hajj H" first="Hiba" last="El Hajj">Hiba El Hajj</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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