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

Zijing Zhou, Xiaonuo Ma, Yiechang Lin, Delfine Cheng, Navid Bavi, Genevieve A. Secker, Jinyuan Vero Li, Vaibhao Janbandhu, Drew L. Sutton, Hamish S. Scott, Mingxi Yao, Richard P. Harvey, Natasha L. Harvey, Ben Corry, Yixiao Zhang*, Charles D. Cox*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)799-804
Number of pages6
JournalScience
Volume381
Issue number6659
DOIs
Publication statusPublished - Aug 2023

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