Optineurin calibrates STING-mediated type I interferon response.

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA, producing cGAMP that activates stimulator of interferon genes (STING).
• STING activation leads to type I interferon (IFN) production, a critical immune response.
• Optineurin (OPTN) is an adaptor protein involved in various cellular processes, including immune signaling.

Purpose of the Study:

• To investigate the role of Optineurin (OPTN) in STING-mediated type I interferon (IFN) responses.
• To determine if OPTN is necessary for STING to mediate type I IFN production.
• To elucidate the interaction between STING and OPTN.

Main Methods:

• Examined STING-mediated type I IFN response in human and mouse cells with modulated OPTN levels.
• Investigated STING-OPTN binding interactions.
• Assessed the engagement of OPTN with STING and TBK1.

Main Results:

• Modulating OPTN levels significantly altered STING-mediated type I IFN responses.
• The N-terminal domain of STING directly binds to the C-terminal ubiquitin-binding domain of OPTN.
• OPTN was found to engage with both STING and TBK1, suggesting a role in the signaling complex.

Conclusions:

• Optineurin (OPTN) plays a crucial role in calibrating the STING-mediated type I interferon (IFN) response.
• OPTN acts as a scaffold, bringing together STING and TBK1 to regulate IFN production.
• Targeting the STING-OPTN interaction could offer therapeutic strategies for autoimmune diseases.