Cell biological insights into human STING variants
Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-localized transmembrane protein. STING induces type I interferon and inflammatory responses against a variety of double-stranded DNA (dsDNA) viruses, which is critical for limiting their infection and replication. In certain set...
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Japan Society for Cell Biology
2025-05-01
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| Series: | Cell Structure and Function |
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| Online Access: | https://www.jstage.jst.go.jp/article/csf/50/1/50_25020/_html/-char/en |
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| author | Shogo Koide Eisuke Yumoto Jun Nakayama Shigeki Higashiyama Yoshihiko Kuchitsu Tomohiko Taguchi |
| author_facet | Shogo Koide Eisuke Yumoto Jun Nakayama Shigeki Higashiyama Yoshihiko Kuchitsu Tomohiko Taguchi |
| author_sort | Shogo Koide |
| collection | DOAJ |
| description | Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-localized transmembrane protein. STING induces type I interferon and inflammatory responses against a variety of double-stranded DNA (dsDNA) viruses, which is critical for limiting their infection and replication. In certain settings where self-DNAs (genomic or mitochondrial DNA) emerge in the cytosol or when intracellular membrane traffic is impaired, STING becomes activated and triggers inflammation, which may contribute to the pathogenesis of various autoinflammatory and neurodegenerative diseases, including COPA syndrome and Parkinson’s disease. The human STING gene exhibits genetic heterogeneity with R232, HAQ (R71H-G230A-R293Q), and H232 being the most common variants, along with population stratification. A very recent study has shown that HAQ, not R232 or H232, mediates complete clinical protection in the pathogenesis of COPA syndrome. These results reveal, for the first time, the distinct activities of the major variants in the context of the pathogenesis of autoinflammatory diseases. Besides these major variants, there exist minor pathogenic STING variants that cause an autoinflammatory disease called STING-associated vasculopathy with onset in infancy (SAVI). This review summarizes recent insights into human STING variants and their inflammatory activities. Key words: innate immunity, STING variants, COPA syndrome, membrane traffic, the Golgi |
| format | Article |
| id | doaj-art-442c98e5f3b24e00a52ffdb64b5cf070 |
| institution | OA Journals |
| issn | 0386-7196 1347-3700 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Japan Society for Cell Biology |
| record_format | Article |
| series | Cell Structure and Function |
| spelling | doaj-art-442c98e5f3b24e00a52ffdb64b5cf0702025-08-20T02:05:18ZengJapan Society for Cell BiologyCell Structure and Function0386-71961347-37002025-05-0150113514410.1247/csf.25020csfCell biological insights into human STING variantsShogo Koide0Eisuke Yumoto1Jun Nakayama2Shigeki Higashiyama3Yoshihiko Kuchitsu4Tomohiko Taguchi5Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityDepartment of Oncogenesis and Growth Regulation, Osaka International Cancer InstituteDepartment of Oncogenesis and Growth Regulation, Osaka International Cancer InstituteLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityStimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-localized transmembrane protein. STING induces type I interferon and inflammatory responses against a variety of double-stranded DNA (dsDNA) viruses, which is critical for limiting their infection and replication. In certain settings where self-DNAs (genomic or mitochondrial DNA) emerge in the cytosol or when intracellular membrane traffic is impaired, STING becomes activated and triggers inflammation, which may contribute to the pathogenesis of various autoinflammatory and neurodegenerative diseases, including COPA syndrome and Parkinson’s disease. The human STING gene exhibits genetic heterogeneity with R232, HAQ (R71H-G230A-R293Q), and H232 being the most common variants, along with population stratification. A very recent study has shown that HAQ, not R232 or H232, mediates complete clinical protection in the pathogenesis of COPA syndrome. These results reveal, for the first time, the distinct activities of the major variants in the context of the pathogenesis of autoinflammatory diseases. Besides these major variants, there exist minor pathogenic STING variants that cause an autoinflammatory disease called STING-associated vasculopathy with onset in infancy (SAVI). This review summarizes recent insights into human STING variants and their inflammatory activities. Key words: innate immunity, STING variants, COPA syndrome, membrane traffic, the Golgihttps://www.jstage.jst.go.jp/article/csf/50/1/50_25020/_html/-char/eninnate immunitysting variantscopa syndromemembrane trafficthe golgi |
| spellingShingle | Shogo Koide Eisuke Yumoto Jun Nakayama Shigeki Higashiyama Yoshihiko Kuchitsu Tomohiko Taguchi Cell biological insights into human STING variants Cell Structure and Function innate immunity sting variants copa syndrome membrane traffic the golgi |
| title | Cell biological insights into human STING variants |
| title_full | Cell biological insights into human STING variants |
| title_fullStr | Cell biological insights into human STING variants |
| title_full_unstemmed | Cell biological insights into human STING variants |
| title_short | Cell biological insights into human STING variants |
| title_sort | cell biological insights into human sting variants |
| topic | innate immunity sting variants copa syndrome membrane traffic the golgi |
| url | https://www.jstage.jst.go.jp/article/csf/50/1/50_25020/_html/-char/en |
| work_keys_str_mv | AT shogokoide cellbiologicalinsightsintohumanstingvariants AT eisukeyumoto cellbiologicalinsightsintohumanstingvariants AT junnakayama cellbiologicalinsightsintohumanstingvariants AT shigekihigashiyama cellbiologicalinsightsintohumanstingvariants AT yoshihikokuchitsu cellbiologicalinsightsintohumanstingvariants AT tomohikotaguchi cellbiologicalinsightsintohumanstingvariants |