@article {8068,
	title = {MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells.},
	journal = {APMIS},
	volume = {123},
	year = {2015},
	month = {2015 Aug},
	pages = {682-7},
	abstract = {<p>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.</p>},
	keywords = {Animals, Cytoplasmic Granules, Exocytosis, Interferon-gamma, Mice, Mice, Inbred C57BL, Mice, Knockout, Microtubule-Associated Proteins, Proteins, T-Lymphocytes, Cytotoxic, Transcription Factors, Up-Regulation},
	issn = {1600-0463},
	doi = {10.1111/apm.12402},
	author = {Boding, Lasse and Hansen, Ann K and Meroni, Germana and Levring, Trine B and Woetmann, Anders and {\O}dum, Niels and Bonefeld, Charlotte M and Geisler, Carsten}
}
@article {8025,
	title = {Midline 1 directs lytic granule exocytosis and cytotoxicity of mouse killer T cells.},
	journal = {Eur J Immunol},
	volume = {44},
	year = {2014},
	month = {2014 Oct},
	pages = {3109-18},
	abstract = {<p>Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2A activity. Loss-of-function mutations in MID1 lead to the X-linked Opitz G/BBB syndrome characterized by defective midline development during embryogenesis. Here, we show that MID1 is strongly upregulated in murine cytotoxic lymphocytes (CTLs), and that it controls TCR signaling, centrosome trafficking, and exocytosis of lytic granules. In accordance, we find that the killing capacity of MID1(-/-) CTLs is impaired. Transfection of MID1 into MID1(-/-) CTLs completely rescued lytic granule exocytosis, and vice versa, knockdown of MID1 inhibited exocytosis of lytic granules in WT CTLs, cementing a central role for MID1 in the regulation of granule exocytosis. Thus, MID1 orchestrates multiple events in CTL responses, adding a novel level of regulation to CTL activation and cytotoxicity.</p>},
	keywords = {Animals, Blotting, Western, Cytotoxicity, Immunologic, Exocytosis, Flow Cytometry, Mice, Mice, Knockout, Mice, Transgenic, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Secretory Vesicles, T-Lymphocytes, Cytotoxic},
	issn = {1521-4141},
	doi = {10.1002/eji.201344388},
	author = {Boding, Lasse and Hansen, Ann K and Meroni, Germana and Johansen, Bo B and Braunstein, Thomas H and Bonefeld, Charlotte M and Kongsbak, Martin and Jensen, Benjamin A H and Woetmann, Anders and Thomsen, Allan R and Odum, Niels and von Essen, Marina R and Geisler, Carsten}
}
