DOI: 10.1073/pnas.042686099. WASp verprolin homology, cofilin homology, and acidic region domain-mediated actin polymerization is required for T cell development

WASp verprolin homology, cofilin homology, and acidic region domain-mediated actin polymerization is required for T cell development

10.1073/pnas.042686099

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

All members of the Wiskott–Aldrich syndrome protein (WASp) family contain a carboxyl-terminal verprolin homology, cofilin homology, and acidic region (VCA) domain that binds and activates the Arp2/3 complex, thereby linking these proteins to the induction of actin polymerization. Although the VCA domain imbues WASp and other WASp family members with the capacity to modulate cytoskeletal organization, little is known about the impact of this domain activity on lymphoid cell function. Here we demonstrate that T cell-restricted expression of VCA domain-deleted WASp (WASpΔVCA) in WAS−/−mice engenders a severe early block in T lymphopoiesis associated with impaired T cell antigen receptor αβ expression and a consequent failure to generate single-positive CD4+and CD8+T cells. These latter defects, which are not observed in WAS−/−mice, are associated with impaired induction of cellular actin polymerization and a failure in the terminal differentiation of double-negative thymocytes. These findings indicate that WASp family proteins play an essential role in modulating the signaling events required for early thymocyte development and reveal their capacity to subserve this role to depend on VCA domain-mediated actin polymerization.

Bibliography

Zhang, J., Shi, F., Badour, K., Deng, Y., McGavin, M. K. H., & Siminovitch, K. A. (2002). WASp verprolin homology, cofilin homology, and acidic region domain-mediated actin polymerization is required for T cell development. Proceedings of the National Academy of Sciences, 99(4), 2240â2245.

Authors 6

Jinyi Zhang (first)
Fabio Shi (additional)
Karen Badour (additional)
Yupu Deng (additional)
Mary K. H. McGavin (additional)
Katherine A. Siminovitch (additional)

References 44 Referenced 33

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:17 a.m.)
Indexed	3 months ago (May 29, 2025, 5:07 a.m.)
Issued	23 years, 6 months ago (Feb. 12, 2002)
Published	23 years, 6 months ago (Feb. 12, 2002)
Published Online	23 years, 6 months ago (Feb. 12, 2002)
Published Print	23 years, 6 months ago (Feb. 19, 2002)

Funders 0

None

BibTeX

@article{Zhang_2002, title={WASp verprolin homology, cofilin homology, and acidic region domain-mediated actin polymerization is required for T cell development}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.042686099}, DOI={10.1073/pnas.042686099}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zhang, Jinyi and Shi, Fabio and Badour, Karen and Deng, Yupu and McGavin, Mary K. H. and Siminovitch, Katherine A.}, year={2002}, month=feb, pages={2240–2245} }

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