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

Zhou, Zijing and Ma, Xiaonuo and Lin, Yiechang and Cheng, Delfine and Bavi, Navid and Secker, Genevieve A. and Li, Jinyuan Vero and Janbandhu, Vaibhao and Sutton, Drew L. and Scott, Hamish S. and Yao, Mingxi and Harvey, Richard P. and Harvey, Natasha L. and Corry, Ben and Zhang, Yixiao and Cox, Charles D. (2023) MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels. Science, 381 (6659). pp.799-804. ISSN 0036-8075

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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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 03 Apr 2024 03:33
Last Modified: 03 Apr 2024 03:33

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