| Title: |
MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells |
| Authors: |
Boding, Lasse; Hansen, Ann K.; Meroni, Germana; Levring, Trine B.; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte M.; Geisler, Carsten |
| Contributors: |
Novo Nordisk; Danmarks Grundforskningsfond; Lundbeckfonden; A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal |
| Source: |
APMIS ; volume 123, issue 8, page 682-687 ; ISSN 0903-4641 1600-0463 |
| Publisher Information: |
Wiley |
| Publication Year: |
2015 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
We have recently shown that the E3 ubiquitin ligase midline 1 ( MID 1) is upregulated in murine cytotoxic lymphocytes ( CTL ), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID 1 knock‐out ( MID 1 −/− ) 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 MID 1 gene knock‐out did not affect exocytosis and cytotoxicity more severely and speculated whether MID 2, a close homologue of MID 1, might partially compensate for the loss of MID 1 in MID 1 −/− CTL . Here, we showed that MID 2, like MID 1, is upregulated in activated murine T cells. Furthermore, MID 1 −/− CTL upregulated MID 2 two–twenty‐fold stronger than CTL from WT mice, suggesting that MID 2 might compensate for MID 1. In agreement, transfection of MID 2 into MID 1 −/− CTL completely rescued exocytosis of lytic granules in MID 1 −/− CTL , and vice versa, knock‐down of MID 2 inhibited exocytosis of lytic granules in both WT and MID 1 −/− CTL , demonstrating that both MID 1 and MID 2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID 1 and MID 2 in CTL . |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/apm.12402 |
| Availability: |
https://doi.org/10.1111/apm.12402; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fapm.12402; https://onlinelibrary.wiley.com/doi/pdf/10.1111/apm.12402 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.7E899859 |
| Database: |
BASE |