Journal
IMMUNITY
Volume 32, Issue 4, Pages 541-556Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2010.03.007
Keywords
-
Categories
Funding
- Wellcome Trust
Ask authors/readers for more resources
Although essential for T cell function, the identity of the T cell receptor inside-out pathway for lymphocyte function-associated antigen 1 (LFA-1) adhesion has proved elusive. Here, we define the inside-out pathway mediated by N-terminal SKAP1 (SKAP-55) domain binding to the C-terminal SARAH domain of RapL. TcR induced Rap1-RapL complex formation and LFA-1 binding failed to occur in Skap1(-/-) primary T cells. SKAP1 generated a SKAP1-RapL-Rap1 complex that bound to LFA-1, whereas a RapL mutation (L224A) that abrogated SKAP1 binding without affecting MST1 disrupted component colocalization in vesicles as well as T cell-dendritic cell (DC) conjugation. RapL expression also slowed T cell motility in D011.10 transgenic T cells in lymph nodes (LNs), an effect reversed by the L224A mutation with reduced dwell times between T cells and DCs. Overall, our findings define a TCR inside-out pathway via N-SKAP1-C-RapL that regulates T cell adhesion, motility, and arrest times with DCs in LNs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available