Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT.
T cell activation induces functional changes in cell shape and cytoskeletal architecture. To facilitate the collection of dynamic, high-resolution images of activated T cells, we plated T cells on coverslips coated with antibodies to the T cell receptor (TCR). Using these images, we were able to quantitate the morphological responses of individual cells over time. Here, we show that TCR engagement triggers the formation and expansion of contacts bounded by continuously remodeled actin-rich rings. These processes are associated with the extension of lamellipodia and require actin polymerization, tyrosine kinase activation, cytoplasmic calcium increases, and LAT, an important hematopoietic adaptor. In addition, the maintenance of the resulting contact requires sustained calcium influxes, an intact microtubule cytoskeleton, and functional LAT.
Bunnell
S C
SC
Laboratory of Cellular and Molecular Biology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
Kapoor
V
V
Trible
R P
RP
Zhang
W
W
Samelson
L E
LE
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001665:Binding Sites; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002352:Carrier Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D007527:Isoenzymes; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D015638:Cytochalasin D; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D003078:Colchicine; D002118:Calcium