![]() ![]() Clinically, these disorders often manifest with neurological features such as encephalopathy, cerebral calcification, leukodystrophy and cerebral atrophy. This dichotomy is particularly well illustrated by the type I interferonopathies, Mendelian diseases characterised by chronically enhanced type I IFN signalling 4, 5. Contrasting with this protective role against viral infection, inappropriate activation of an IFN response is pathogenic, eventually leading to tissue damage 4. Type I interferon (IFN) mediated innate immunity constitutes an essential element in the response to viral infection, establishing an anti-viral state through the upregulation of hundreds of IFN stimulated genes (ISGs) 1, 2, 3. Our data show an unexpected dual role of ARF1 in maintaining cGAS-STING homeostasis, through promotion of mitochondrial integrity and STING recycling. Mechanistically, mutated ARF1 perturbs mitochondrial morphology, causing cGAS activation by aberrant mitochondrial DNA release, and leads to accumulation of active STING at the Golgi/ERGIC due to defective retrograde transport. Disease-associated, GTPase-defective ARF1 increases cGAS-STING dependent type I IFN signalling in cell lines and primary patient cells. Heterozygous ARF1 missense mutations cause a previously unrecognized type I interferonopathy associated with enhanced IFN-stimulated gene expression. ![]() Here, we identify the GTPase ADP-ribosylation factor 1 (ARF1) as a crucial negative regulator of cGAS-STING signalling. Termination is achieved through autophagic degradation or recycling of STING by retrograde Golgi-to-ER transport. Upon recognition of DNA by cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) translocates along the endoplasmic reticulum (ER)-Golgi axis to induce IFN signalling. Type I interferon (IFN) signalling is tightly controlled. Nature Communications volume 14, Article number: 6770 ( 2023) Account fees (e.g., monthly service, overdraft) may apply to Wells Fargo account(s) with which you use Zelle ®.ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling Your mobile carrier's message and data rates may apply. ![]() For more information, view the Zelle ® Transfer Service Addendum to the Wells Fargo Online Access Agreement. To send or receive money with a small business, both parties must be enrolled with Zelle ® directly through their financial institution’s online or mobile banking experience. Payment requests to persons not already enrolled with Zelle ® must be sent to an email address. The Request feature within Zelle ® is only available through Wells Fargo using a smartphone. Neither Wells Fargo nor Zelle ® offers purchase protection for payments made with Zelle ® - for example, if you do not receive the item you paid for or the item is not described or as you expected. For your protection, Zelle ® should only be used for sending money to friends, family, or others you trust. Transactions between enrolled users typically occur in minutes. checking or savings account required to use Zelle ®. Enrollment with Zelle ® through Wells Fargo Online ® or Wells Fargo Business Online ® is required. ![]()
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