title: Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production.
abstract: 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.
authors.affiliation: Program in Immunology, Tufts University, Boston, MA 02111;
authors.forename: Guy
authors.initials: G
authors.lastname: Surpris
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Jennie
authors.initials: J
authors.lastname: Chan
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Mikayla
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia 185910;
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ilyukha
authors.affiliation: Program in Immunology, Tufts University, Boston, MA 02111;
authors.forename: Beiyun C
authors.initials: BC
authors.lastname: Liu
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Maninjay
authors.initials: M
authors.lastname: Atianand
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Shruti
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia 185910;
authors.forename: Tatyana
authors.initials: T
authors.lastname: Volkova
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111; and.
authors.forename: Irina
authors.initials: I
authors.lastname: Smirnova
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: Program in Immunology, Tufts University, Boston, MA 02111; Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia 185910; Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111; and Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 Alexander.Poltorak@tufts.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Poltorak
mesh_terms: D000483:Alleles; D000818:Animals; D004247:DNA / Q000276:immunology; D007370:Interferon Type I / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D009154:Mutation; D021381:Protein Transport / Q000502:physiology; D000099197:STING Protein
chemical_list: D004247:DNA; D007370:Interferon Type I; D008565:Membrane Proteins; C530855:Sting1 protein, mouse; D000099197:STING Protein