CD45 signals outside of lipid rafts to promote ERK activation, synaptic raft clustering, and IL-2 production.
CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation, although the molecular consequences of CD45 repositioning remain unclear. In this study we examine the role of CD45 membrane compartmentalization in regulating murine T cell activation. We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. We propose that these dual CD45 activities ensure that only robust TCR signals proceed, whereas signals meeting threshold requirements are potentiated. Our findings highlight membrane compartmentalization as a key regulator of CD45 function and elucidate a novel signal transduction pathway by which raft-excluded CD45 positively regulates T cell activation.
Zhang
Min
M
Department of Microbiology, University of California School of Medicine, Los Angeles, CA 90095, USA.
Moran
Miriana
M
Round
June
J
Low
Teresa A
TA
Patel
Viresh P
VP
Tomassian
Tamar
T
Hernandez
Joseph D
JD
Miceli
M Carrie
MC
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D020664:Son of Sevenless Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology; D018909:src Homology Domains / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D007376:Interleukin-2; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D020664:Son of Sevenless Proteins; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens