T-cell integrins: more than just sticking points.
T cells use integrins in essentially all of their functions. They use integrins to migrate in and out of lymph nodes and, following infection, to migrate into other tissues. At the beginning of an immune response, integrins also participate in the immunological synapse formed between T cells and antigen-presenting cells. Because the ligands for integrins are widely expressed, integrin activity on T cells must be tightly controlled. Integrins become active following signalling through other membrane receptors, which cause both affinity alteration and an increase in integrin clustering. Lipid raft localization may increase integrin activity. Signalling pathways involving ADAP, Vav-1 and SKAP-55, as well as Rap1 and RAPL, cause clustering of leukocyte function-associated antigen-1 (LFA-1; integrin alphaLbeta2). T-cell integrins can also signal, and the pathways dedicated to the migratory activity of T cells have been the most investigated so far. Active LFA-1 causes T-cell attachment and lamellipodial movement induced by myosin light chain kinase at the leading edge, whereas RhoA and ROCK cause T-cell detachment at the trailing edge. Another important signalling pathway acts through CasL/Crk, which might regulate the activity of the GTPases Rac and Rap1 that have important roles in T-cell migration.
Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK. nancy.hogg@cancer.org.uk
Nancy
N
Hogg
Melanie
M
Laschinger
Katherine
K
Giles
Alison
A
McDowall
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000096985:Calponins
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C455272:MICAL1 protein, human; D000096985:Calponins