Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton.
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.
Barda-Saad
Mira
M
Laboratory of Cellular and Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Braiman
Alex
A
Titerence
Rachel
R
Bunnell
Stephen C
SC
Barr
Valarie A
VA
Samelson
Lawrence E
LE
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D018929:Cell Culture Techniques; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D017027:Protein Tyrosine Phosphatases