CD45 signals outside of lipid rafts to promote ERK activation, synaptic raft clustering, and IL-2 production |
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Authors: | Zhang Min Moran Miriana Round June Low Teresa A Patel Viresh P Tomassian Tamar Hernandez Joseph D Miceli M Carrie |
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Affiliation: | Department of Microbiology, University of California School of Medicine, Los Angeles, CA 90095, USA. |
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Abstract: | 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. |
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