Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton

Mira Barda-Saad, Alex Braiman, Rachel Titerence, Stephen C. Bunnell, Valarie A. Barr, Lawrence E. Samelson

Research output: Contribution to journalArticlepeer-review

267 Scopus citations

Abstract

T cell receptor (TCR) engagement leads to actin polymerization at the site of T cell contact with antigen-presenting cells. Here we have studied the dynamic activity of proteins involved in regulating actin polymerization in live T cells after activation. Two such adaptor proteins, Nck and the Wiskott-Aldrich syndrome protein (WASp), were recruited to the TCR during initial T cell activation, where they colocalized with the tyrosine kinase Zap70. The recruitment of Nck and WASp depended on TCR-induced tyrosine phosphorylation and the LAT and SLP-76 adaptors. Nck and WASp migrated peripherally and accumulated at an actin-rich circumferential ring. Thus, actin polymerization regulated by the TCR begins at the TCR. Molecules recruited to the TCR regulate actin polymerization and this process drives plasma membrane movement and cellular spreading.

Original languageEnglish
Pages (from-to)80-89
Number of pages10
JournalNature Immunology
Volume6
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank S. Saitoh and D. Mahadeo for their help; S. Garfield and S. Wincovitch for their help in the operation of the LSM 510; B. Taylor for cell sorting; and P. Schwartzberg and C. Sommers for reading the manuscript. Supported by the Cancer Research Institute (S.C.B.) and the Office of Research on Women’s Health, Foundation for Advanced Education in the Sciences, National Institutes of Health (R.T.).

Funding

The authors thank S. Saitoh and D. Mahadeo for their help; S. Garfield and S. Wincovitch for their help in the operation of the LSM 510; B. Taylor for cell sorting; and P. Schwartzberg and C. Sommers for reading the manuscript. Supported by the Cancer Research Institute (S.C.B.) and the Office of Research on Women’s Health, Foundation for Advanced Education in the Sciences, National Institutes of Health (R.T.).

FundersFunder number
Office of Research on Women’s Health, Foundation for Advanced Education in the Sciences
National Institutes of Health
National Cancer InstituteZ01BC010304
Cancer research institute

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