IMMUNOLOGY2026™ Conference Recordings For Attendees-Tuning Innate Immune Signaling Through Ion Channels: Regulation of cGAMP-STING by Puromycin-Sensitive Aminopeptidase

Tuning Innate Immune Signaling Through Ion Channels: Regulation of cGAMP-STING by Puromycin-Sensitive Aminopeptidase

Video Transcription

Video Summary

Dr. Zhao Xu described how a volume-regulated anion channel family member, LRRC8/VRAC, can pass cyclic GMP-AMP (cGAMP), linking ion channel biology to innate immunity. His lab found that puromycin-sensitive aminopeptidase (PSA) binds the channel’s intracellular leucine-rich repeat domain, stabilizing it and strongly inhibiting channel activity. Structural studies showed PSA’s binding, not its peptidase enzyme function, mediates this effect. Knocking out PSA increased basal channel activity, boosted cGAMP uptake in immune cells, and enhanced STING signaling. In tumor cells, PSA loss also increased cGAMP release, amplifying downstream immune activation. Xu proposed PSA as a dual regulator that dampens both cGAMP release from producer cells and uptake by recipient immune cells, making it a potential therapeutic target for boosting anti-tumor innate immune signaling.

Meta Tag

Date April 16, 2026 8:00 AM - 9:30 AM

Room 104C

Session New Insights into the Role of Ion Channels and Transporters in Immunity, Sponsored by the Society of General Physiologists

Speaker Zhaozhu Qiu

Track Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Year 2026

Keywords

LRRC8/VRAC

cGAMP

puromycin-sensitive aminopeptidase

PSA

STING signaling

innate immunity

April 16, 2026 8:00 AM - 9:30 AM

104C

New Insights into the Role of Ion Channels and Transporters in Immunity, Sponsored by the Society of General Physiologists

Zhaozhu Qiu

Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

2026