期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 8, 页码 2132-2141出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201242525
关键词
Centrosome; Cytotoxic T lymphocytes; Immunological synapse; Nucleus; Polarization
类别
资金
- Wellcome Trust [075880]
Cytotoxic T lymphocytes (CTLs) kill tumorigenic and virally infected cells by targeted secretion of lytic granule contents. The precise point at which secretion occurs is directed by the centrosome docking at the immunological synapse (IS). The centrosome is highly dynamic in CTLs, lagging behind the nucleus in the uropod of migrating CTLs, but translocating across the entire length of the cell to dock at the IS when a target cell is recognized. While in most cell types, the centrosome is always closely associated with the nuclear membrane, in CTLs, it often appears to be dissociated from the nucleus, both in migrating cells and when forming an IS. We asked whether this dissociation is required for CTL killing, by expressing GFP-BICD2-NT-nesprin-3, which tethers the centrosome to the nucleus irreversibly. Immunofluorescence microscopy revealed that the centrosome polarized successfully to the central supramolecular activation complex (cSMAC) of the synapse in GFP-BICD2-NT-nesprin-3-expressing CTLs, with the centrosome and nucleus migrating together to the IS. CTLs in which the centrosome was glued to the nucleus were able to dock and release granules at the IS as effectively as mock-treated cells. These data demonstrate that CTL cytotoxicity is independent of centrosomal dissociation from the nuclear envelope.
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