MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells
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MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells. / Boding, Lasse; Hansen, Ann K; Meroni, Germana; Levring, Trine B; Andersen, Anders Woetmann; Ødum, Niels; Bonefeld, Charlotte M; Geisler, Carsten.
In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, Vol. 123, No. 8, 08.2015, p. 682-7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells
AU - Boding, Lasse
AU - Hansen, Ann K
AU - Meroni, Germana
AU - Levring, Trine B
AU - Andersen, Anders Woetmann
AU - Ødum, Niels
AU - Bonefeld, Charlotte M
AU - Geisler, Carsten
N1 - © 2015 APMIS. Published by John Wiley & Sons Ltd.
PY - 2015/8
Y1 - 2015/8
N2 - 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.
AB - 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.
KW - Animals
KW - Cytoplasmic Granules
KW - Exocytosis
KW - Interferon-gamma
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Microtubule-Associated Proteins
KW - Proteins
KW - T-Lymphocytes, Cytotoxic
KW - Transcription Factors
KW - Up-Regulation
U2 - 10.1111/apm.12402
DO - 10.1111/apm.12402
M3 - Journal article
C2 - 25924778
VL - 123
SP - 682
EP - 687
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 8
ER -
ID: 158578325