Paxillin associates with the microtubule cytoskeleton and the immunological synapse of CTL through its LD domains and contributes to microtubule organizing center reorientation (112.24)
| Autor: | Hanne Ostergaard, Leslie Robertson |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:112.24-112.24 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.112.24 |
| Popis: | The cytoskeletal adaptor protein paxillin localizes to the microtubule organizing center (MTOC) in T cells and upon target cell binding is recruited to the supramolecular activation complex (SMAC). We mapped the region of paxillin that associates with both the MTOC and SMAC to the leucine-aspartic acid (LD) domains and showed that a protein segment containing LD2-4 was sufficient for MTOC and SMAC recruitment. Paxillin localizes to the peripheral area of the SMAC along with LFA-1 suggesting that LFA-1 may contribute to its recruitment. To test this possibility, beads coated with anti-CD3 were used alongside non-antigen bearing target cells, thus physically separating adhesion and TCR signals. Paxillin preferentially localized to sites of integrin engagement rather than to sites of TCR engagement, further suggesting that LFA-1 contributes to paxillin recruitment. These sites of antigen-independent integrin binding were not sufficient to induce MTOC reorientation. Paxillin has been shown to be phosphorylated downstream of ERK, but when we generated a mutation that abolished detectable phosphorylation we found that paxillin still bound to the MTOC and was recruited to the SMAC. Finally, expression of the LD2-4 region of paxillin reduced MTOC reorientation. These studies demonstrate that paxillin is recruited, through its LD domains, to sites of integrin engagement and may contribute to CTL adhesion and subsequent MTOC reorientation required for directional degranulation. |
| Databáze: | OpenAIRE |
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