Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production
| Autor: | Maninjay K. Atianand, Katherine A. Fitzgerald, Jennie Chan, Tatyana O. Volkova, Beiyun C. Liu, Alexander Poltorak, Shrutie Sharma, Mikayla R. Thompson, Vladimir Ilyukha, Irina Smirnova, Guy Surpris |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Immunology Biology medicine.disease_cause Article 03 medical and health sciences Mice medicine Immunology and Allergy Animals Allele Gene Alleles Genetics Mice Knockout Mutation Microscopy Confocal Endoplasmic reticulum Membrane Proteins DNA Virology eye diseases Mice Mutant Strains Transport protein Mice Inbred C57BL Sting Protein Transport 030104 developmental biology Membrane protein Interferon Type I Interferon type I medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 196(2) |
| ISSN: | 1550-6606 |
| Popis: | With the stimulator of IFN genes (STING) C terminus being extensively studied, the role of the N-terminal domain (NTD) of STING remains an important subject of investigation. In this article, we identify novel mutations in NTD of Sting of the MOLF strain in response to HSV and Listeria monocytogenes both in vitro and in vivo. These mutations are responsible for low levels of IFN-β caused by failure of MOLF STING to translocate from the endoplasmic reticulum. These data provide evidence that the NTD of STING affects DNA responses via control of trafficking. They also show that the genetic diversity of wild-derived mice resembles the diversity observed in humans. Several human alleles of STING confer attenuated IFN-I production similar to what we observe with the MOLF Sting allele, a crucial functional difference not apparent in classical inbred mice. Thus, understanding the functional significance of polymorphisms in MOLF STING can provide basic mechanistic insights relevant to humans. |
| Databáze: | OpenAIRE |
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