AustralieFrV1, PubMed, Curation, bibRecord, 000407

Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection.

Identifieur interne : 000407 ( PubMed/Curation ); précédent : 000406; suivant : 000408

Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection.

Auteurs : Anne Garreau ; Gaëtan Blaize ; Jérémy Argenty ; Nelly Rouquié ; Audrey Tourdès ; Stephen A. Wood [Australie] ; Abdelhadi Saoudi ; Renaud Lesourne [France]

Source :

Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2017.

RBID : pubmed:28877990

Descripteurs français

English descriptors

KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Animals, Cell Differentiation, Cells, Cultured, Clonal Selection, Antigen-Mediated, Endopeptidases (metabolism), GRB2 Adaptor Protein (metabolism), Lymphocyte Activation, Membrane Proteins (metabolism), Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphoproteins (metabolism), Precursor Cells, T-Lymphoid (physiology), Protein Binding, Protein Stability, Proteins (genetics), Proteins (metabolism), Receptors, Antigen, T-Cell (metabolism), T-Lymphocytes (physiology), Thymus Gland (immunology).
MESH :
- chemical , genetics : Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Endopeptidases, GRB2 Adaptor Protein, Membrane Proteins, Phosphoproteins, Proteins, Receptors, Antigen, T-Cell.
- immunology : Thymus Gland.
- physiology : Precursor Cells, T-Lymphoid, T-Lymphocytes.
- Animals, Cell Differentiation, Cells, Cultured, Clonal Selection, Antigen-Mediated, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Binding, Protein Stability.

Abstract

Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection. We show in this article that Themis protein expression is increased in double-positive thymocytes undergoing positive selection and is sustained in immature single-positive thymocytes, despite the strong decrease in Themis mRNA levels in these subsets. We found that Themis stability is controlled by the ubiquitin-specific protease USP9X, which removes ubiquitin K48-linked chains on Themis following TCR engagement. Biochemical analyses indicate that USP9X binds directly to the N-terminal CABIT domain of Themis and indirectly to the adaptor protein Grb2, with the latter interaction enabling recruitment of Themis/USP9X complexes to LAT, thereby sustaining Themis expression following positive selection. Together, these data suggest that TCR-mediated signals enhance Themis stability upon T cell development and identify USP9X as a key regulator of Themis protein turnover.

DOI: 10.4049/jimmunol.1700566
PubMed: 28877990

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Anne Garreau

<affiliation><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, CNRS, INSERM, UPS, 31024 Toulouse, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Gaëtan Blaize

<affiliation><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, CNRS, INSERM, UPS, 31024 Toulouse, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Jérémy Argenty

<affiliation><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, CNRS, INSERM, UPS, 31024 Toulouse, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Nelly Rouquié

<affiliation><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, CNRS, INSERM, UPS, 31024 Toulouse, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Audrey Tourdès

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<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Abdelhadi Saoudi

<affiliation><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, CNRS, INSERM, UPS, 31024 Toulouse, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>

Le document en format XML

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<front><div type="abstract" xml:lang="en">Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection. We show in this article that Themis protein expression is increased in double-positive thymocytes undergoing positive selection and is sustained in immature single-positive thymocytes, despite the strong decrease in Themis mRNA levels in these subsets. We found that Themis stability is controlled by the ubiquitin-specific protease USP9X, which removes ubiquitin K48-linked chains on Themis following TCR engagement. Biochemical analyses indicate that USP9X binds directly to the N-terminal CABIT domain of Themis and indirectly to the adaptor protein Grb2, with the latter interaction enabling recruitment of Themis/USP9X complexes to LAT, thereby sustaining Themis expression following positive selection. Together, these data suggest that TCR-mediated signals enhance Themis stability upon T cell development and identify USP9X as a key regulator of Themis protein turnover.</div>
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<Abstract><AbstractText>Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection. We show in this article that Themis protein expression is increased in double-positive thymocytes undergoing positive selection and is sustained in immature single-positive thymocytes, despite the strong decrease in Themis mRNA levels in these subsets. We found that Themis stability is controlled by the ubiquitin-specific protease USP9X, which removes ubiquitin K48-linked chains on Themis following TCR engagement. Biochemical analyses indicate that USP9X binds directly to the N-terminal CABIT domain of Themis and indirectly to the adaptor protein Grb2, with the latter interaction enabling recruitment of Themis/USP9X complexes to LAT, thereby sustaining Themis expression following positive selection. Together, these data suggest that TCR-mediated signals enhance Themis stability upon T cell development and identify USP9X as a key regulator of Themis protein turnover.</AbstractText>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>EC 3.4.99.-</RegistryNumber>
<NameOfSubstance UI="C404328">Usp9x protein, mouse</NameOfSubstance>
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</ChemicalList>
<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D048868" MajorTopicYN="N">Adaptor Proteins, Signal Transducing</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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<MeshHeading><DescriptorName UI="D051380" MajorTopicYN="N">GRB2 Adaptor Protein</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D010750" MajorTopicYN="N">Phosphoproteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054504" MajorTopicYN="N">Precursor Cells, T-Lymphoid</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
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</MeshHeading>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D011506" MajorTopicYN="N">Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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<MeshHeading><DescriptorName UI="D011948" MajorTopicYN="N">Receptors, Antigen, T-Cell</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013950" MajorTopicYN="N">Thymus Gland</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year>
<Month>04</Month>
<Day>20</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>08</Month>
<Day>10</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2017</Year>
<Month>9</Month>
<Day>8</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>11</Month>
<Day>2</Day>
<Hour>6</Hour>
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</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2017</Year>
<Month>9</Month>
<Day>8</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">28877990</ArticleId>
<ArticleId IdType="pii">jimmunol.1700566</ArticleId>
<ArticleId IdType="doi">10.4049/jimmunol.1700566</ArticleId>
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   |texte=   Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection.
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	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur les relations entre la France et l'Australie

Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection.

Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection.

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