The actin regulator coronin-1A is mutated in a thymic egress deficient mouse strain and in a T−B+NK+ SCID patient
| Autor: | Shiow, Lawrence R., Roadcap, David W., Paris, Kenneth, Watson, Susan R., Grigorova, Irina L., Lebet, Tonya, An, Jinping, Xu, Ying, Jenne, Craig N., Föger, Niko, Sorensen, Ricardo U., Goodnow, Christopher C., Bear, James E., Puck, Jennifer M., Cyster, Jason G. |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Mice carrying the recessive peripheral T cell deficiency (Ptcd) locus have a block in thymic egress but the mechanism responsible is undefined. Here we found that Ptcd T cells have an intrinsic migration defect, impaired lymphoid tissue trafficking and irregularly shaped protrusions. Characterization of the Ptcd locus revealed an E26K point mutation within the actin regulator coronin-1A (Coro1a) that enhanced its inhibition of the actin regulator Arp2/3 and resulted in its mislocalization from the leading edge of migrating T cells. Discovery of another Coro1a mutant during an N-ethyl-N-nitrosourea (ENU) mutagenesis screen for T cell lymphopenic mice prompted us to evaluate a T cell-deficient, B cell- and NK cell-sufficient (T−B+NK+) severe combined immunodeficiency (SCID) patient, whom we found had mutations in both CORO1A alleles. These findings establish a role for coronin-1A in T cell egress, identify a surface of coronin involved in Arp2/3 regulation, and reveal actin regulation as a biological process defective in human and mouse SCID. |
| Databáze: | OpenAIRE |
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