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Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells.

ABSTRACT: Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression in thymocytes blocks progression from double-positive immature thymocytes, resulting in complete absence of CD4(+) single-positive thymocytes and severe reduction of CD3(+)CD8(+) single-positive thymocytes. Analysis of the contribution of AP-1 deficiency on the interaction between mature CD4(+) T cells and antigen-presenting cells revealed that AP-1 is essential to efficient immune synapse formation and associated T cell activation, suggesting a possible mechanism of AP-1 function in thymocyte development.

SUBMITTER: Alvarez Arias DA

PROVIDER: S-EPMC2823916 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells.

Alvarez Arias Diana A DA McCarty Nami N Lu Linrong L Maldonado Roberto A RA Shinohara Mari L ML Cantor Harvey H

Proceedings of the National Academy of Sciences of the United States of America 20100125 6

Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression in thymocytes blocks progression from double-positive immature thymocytes, resulting in complete absence of CD4(+) single-positive thymocytes and severe reduction of CD3(+)CD8(+) ...[more]

PMID: 20133794

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