MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels

• 成果类型: Article
• 署名作者: Zhou, Zijing; Ma, Xiaonuo; Lin, Yiechang; Cheng, Delfine; Bavi, Navid; Secker, Genevieve A.; Li, Jinyuan Vero; Janbandhu, Vaibhao; Sutton, Drew L.; Scott, Hamish S.; Yao, Mingxi; Harvey, Richard P.; Harvey, Natasha L.; Corry, Ben; Zhang, Yixiao; Cox, Charles D.
• 署名单位: Victor Chang Cardiac Research Institute; University of New South Wales Sydney; Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; Australian National University; University of Chicago; Centre for Cancer Biology; University of South Australia; SA Pathology; University of Adelaide; SA Pathology; Southern University of Science & Technology; University of New South Wales Sydney; University of New South Wales Sydney
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11057
• DOI: 10.1126/science.adh8190
• 发表日期: 2023-08-18
• 页码: 799-804
• 关键词: domain; software

摘要

Piezo channels are critical cellular sensors of mechanical forces. Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few Piezo channel-binding proteins have emerged. In this work, we found that MyoD (myoblast determination)-family inhibitor proteins (MDFIC and MDFI) are PIEZO1/2 interacting partners. These transcriptional regulators bind to PIEZO1/2 channels, regulating channel inactivation. Using single-particle cryogenic electron microscopy, we mapped the interaction site in MDFIC to a lipidated, C-terminal helix that inserts laterally into the PIEZO1 pore module. These Piezo-interacting proteins fit all the criteria for auxiliary subunits, contribute to explaining the vastly different gating kinetics of endogenous Piezo channels observed in many cell types, and elucidate mechanisms potentially involved in human lymphatic vascular disease.