SCIENCE@home

The actin regulator coronin-1A is mutated in a thymic egress deficient mouse strain and in a T−B+NK+ SCID patient

L. Shiow,D. W. Roadcap,K. Paris,S. Watson,I. Grigorova,Tonya Lebet,Jinping An,Ying Xu,C. Jenne,N. Föger,R. Sorensen,C. Goodnow,J. Bear,J. Puck,J. Cyster

Published 2008 in Nature Immunology

ABSTRACT

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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-39 of 39 references · Page 1 of 1

CITED BY

Showing 1-100 of 222 citing papers · Page 1 of 3

123
Next