Abstract
We have recently shown that the E3 ubiquitin ligase midline 1 (MID1) is upregulated in murine cytotoxic lymphocytes (CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out (MID1(-/-)) mice have a 25-30% reduction in exocytosis of lytic granules and cytotoxicity compared to CTL from wild-type (WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1(-/-) CTL. Here, we showed that MID2, like MID1, is upregulated in activated murine T cells. Furthermore, MID1(-/-) CTL upregulated MID2 two-twenty-fold stronger than CTL from WT mice, suggesting that MID2 might compensate for MID1. In agreement, transfection of MID2 into MID1(-/-) CTL completely rescued exocytosis of lytic granules in MID1(-/-) CTL, and vice versa, knock-down of MID2 inhibited exocytosis of lytic granules in both WT and MID1(-/-) CTL, demonstrating that both MID1 and MID2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID1 and MID2 in CTL.
| Original language | English |
|---|---|
| Journal | APMIS : acta pathologica, microbiologica, et immunologica Scandinavica |
| Volume | 123 |
| Issue number | 8 |
| Pages (from-to) | 682-7 |
| Number of pages | 6 |
| ISSN | 0903-4641 |
| DOIs | |
| Publication status | Published - 1 Aug 2015 |
Keywords
- Animals
- Cytoplasmic Granules
- Exocytosis
- Interferon-gamma
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microtubule-Associated Proteins
- Proteins
- T-Lymphocytes, Cytotoxic
- Transcription Factors
- Up-Regulation