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Title[redir]:
Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation | Nature Immunology
Description:
Chaperone-mediated autophagy selectively targets single cytoplasmic proteins for degradation. Macian and colleagues show that such autophagy is induced by engagement of the TCR to target negative regulators of T cell activation. Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation.
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Keywords {๐}
pubmed, google, scholar, cas, cells, cell, autophagy, mice, central, control, chaperonemediated, cuervo, nature, activated, lysosomal, rcan, immunol, degradation, itch, lacko, lampa, hours, article, activation, expression, nat, experiments, dice, supplementary, immunoblot, data, cma, access, biol, meansem, expressing, macian, proteins, selective, assessed, littermate, function, content, aging, med, transfected, cookies, immunology, responses, gene,
Topics {โ๏ธ}
nature portfolio permissions reprints specific research cores privacy policy basic research advertising nature mammalian development chaperone-mediated autophagy regulates track chaperone-mediated autophagy deficient chaperone-mediated autophagy total ฮฒ-hexosaminidase activity fyn-mediated tyrosine phosphorylation calcineurinโnfat signaling network inactivated cma-targeting motifs gene encoding lamp-2a plate bound anti-cd3 author correspondence maintain activation-induced responses social media plasmid-encoded tagged rcan1 myeloid-derived suppressor cells plasmid-encoded tagged itch lamp-2a null mice mouse lamp2a mrna springerlink instant access lamp-2a-deficient mice calcineurin-dependent gene expression permissions chaperone-mediated autophagy media anti-listeria immunoglobulin levels ignacio guerrero-ros thymus-dependent humoral immunity plasmids expressing gfp privacy activation-induced responses myc-tagged-rcan1 competing financial interests introducing molecular chaperones autophagy gene atg5 lentiviral vectors expressing plasmids expressing itch plasmid expressing gfp e3 ubiquitin ligases plate bound anticd3 control litter mate impaired cma activity age-related decline cell receptor signaling
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headline:Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation
description:Chaperone-mediated autophagy selectively targets single cytoplasmic proteins for degradation. Macian and colleagues show that such autophagy is induced by engagement of the TCR to target negative regulators of T cell activation. Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation.
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