%0 Journal Article %J APMIS %D 2015 %T MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells. %A Boding, Lasse %A Hansen, Ann K %A Meroni, Germana %A Levring, Trine B %A Woetmann, Anders %A Ă˜dum, Niels %A Bonefeld, Charlotte M %A Geisler, Carsten %K Animals %K Cytoplasmic Granules %K Exocytosis %K Interferon-gamma %K Mice %K Mice, Inbred C57BL %K Mice, Knockout %K Microtubule-Associated Proteins %K Proteins %K T-Lymphocytes, Cytotoxic %K Transcription Factors %K Up-Regulation %X

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.

%B APMIS %V 123 %P 682-7 %8 2015 Aug %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/25924778?dopt=Abstract %R 10.1111/apm.12402