PMID- 20346707 OWN - NLM STAT- MEDLINE DCOM- 20100506 LR - 20230620 IS - 1097-4180 (Electronic) IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 32 IP - 4 DP - 2010 Apr 23 TI - T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. PG - 541-56 LID - 10.1016/j.immuni.2010.03.007 [doi] AB - 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. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Raab, Monika AU - Raab M AD - Cell Signaling Section, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge UK, CB2 1Q. FAU - Wang, Hongyan AU - Wang H FAU - Lu, Yuning AU - Lu Y FAU - Smith, Xin AU - Smith X FAU - Wu, Zhonglin AU - Wu Z FAU - Strebhardt, Klaus AU - Strebhardt K FAU - Ladbury, John E AU - Ladbury JE FAU - Rudd, Christopher E AU - Rudd CE LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 092627/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100325 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Lymphocyte Function-Associated Antigen-1) RN - 0 (Phosphoproteins) RN - 0 (RAPL protein, mouse) RN - 0 (RASSF5 protein, human) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (SKAP1 protein, human) RN - 0 (SKAP1 protein, mouse) RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) RN - EC 3.6.5.2 (rap1 GTP-Binding Proteins) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Apoptosis Regulatory Proteins MH - Cell Adhesion MH - Cell Movement MH - Cells, Cultured MH - Dendritic Cells/immunology MH - Lymph Nodes/cytology/*immunology/metabolism MH - Lymphocyte Function-Associated Antigen-1/immunology/metabolism MH - Mice MH - Mice, Knockout MH - Monomeric GTP-Binding Proteins/genetics/immunology/*metabolism MH - Mutation MH - Phosphoproteins/deficiency/genetics/*immunology/*metabolism MH - Protein Binding MH - Protein Transport MH - Receptors, Antigen, T-Cell/*immunology/metabolism MH - Signal Transduction MH - T-Lymphocytes/cytology/*immunology/metabolism MH - rap1 GTP-Binding Proteins/immunology/*metabolism PMC - PMC3812847 MID - EMS54931 OID - NLM: EMS54931 EDAT- 2010/03/30 06:00 MHDA- 2010/05/07 06:00 PMCR- 2013/10/30 CRDT- 2010/03/30 06:00 PHST- 2009/05/03 00:00 [received] PHST- 2009/11/05 00:00 [revised] PHST- 2010/01/15 00:00 [accepted] PHST- 2010/03/30 06:00 [entrez] PHST- 2010/03/30 06:00 [pubmed] PHST- 2010/05/07 06:00 [medline] PHST- 2013/10/30 00:00 [pmc-release] AID - S1074-7613(10)00090-7 [pii] AID - 10.1016/j.immuni.2010.03.007 [doi] PST - ppublish SO - Immunity. 2010 Apr 23;32(4):541-56. doi: 10.1016/j.immuni.2010.03.007. Epub 2010 Mar 25.