The actin regulator coronin 1A is mutant in a thymic egress–deficient mouse strain and in a patient with severe combined immunodeficiency
| العنوان: | The actin regulator coronin 1A is mutant in a thymic egress–deficient mouse strain and in a patient with severe combined immunodeficiency |
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| المؤلفون: | David W. Roadcap, Ricardo U. Sorensen, Christopher C. Goodnow, Jason G. Cyster, Tonya Lebet, Susan R. Watson, Craig N. Jenne, Jennifer M. Puck, Ying Xu, Lawrence R. Shiow, James E. Bear, Kenneth Paris, Irina L. Grigorova, Jinping An, Niko Föger |
| المصدر: | Nature immunology, vol 9, iss 11 |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, T-Lymphocytes, Knockout, T cell, Immunology, Mutant, Coronin, Glutamic Acid, Thymus Gland, macromolecular substances, Biology, Actin-Related Protein 2-3 Complex, Gene product, Mice, Cell Movement, Mutant protein, medicine, 2.1 Biological and endogenous factors, Animals, Humans, Immunology and Allergy, Aetiology, Cell Shape, Alleles, Actin, Severe combined immunodeficiency, Lysine, Microfilament Proteins, medicine.disease, Inbred ICR, Molecular biology, T cell deficiency, Actins, medicine.anatomical_structure, Amino Acid Substitution, Mutation, biology.protein, Severe Combined Immunodeficiency, Female |
| الوصف: | Mice carrying the recessive locus for peripheral T cell deficiency (Ptcd) have a block in thymic egress, but the mechanism responsible is undefined. Here we found that Ptcd T cells had an intrinsic migration defect, impaired lymphoid tissue trafficking and irregularly shaped protrusions. Characterization of the Ptcd locus showed a point substitution of lysine for glutamic acid at position 26 in the actin regulator coronin 1A that enhanced its inhibition of the actin regulator Arp2/3 and resulted in its mislocalization from the leading edge of migrating T cells. The discovery of another coronin 1A mutant during an N-ethyl-N-nitrosourea-mutagenesis screen for T cell-lymphopenic mice prompted us to evaluate a T cell-deficient, B cell-sufficient and natural killer cell-sufficient patient with severe combined immunodeficiency, whom we found had mutations in both CORO1A alleles. Our findings establish a function for coronin 1A in T cell egress, identify a surface of coronin involved in Arp2/3 regulation and demonstrate that actin regulation is a biological process defective in human and mouse severe combined immunodeficiency. |
| وصف الملف: | application/pdf |
| تدمد: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni.1662 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2963b97969eb97437027c9e3e073f566 https://doi.org/10.1038/ni.1662 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2963b97969eb97437027c9e3e073f566 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292916 15292908 |
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| DOI: | 10.1038/ni.1662 |