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https://hdl.handle.net/2440/141457
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Type: | Journal article |
Title: | MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels |
Author: | Zhou, Z. Ma, X. Lin, Y. Cheng, D. Bavi, N. Secker, G.A. Li, J.V. Janbandhu, V. Sutton, D.L. Scott, H.S. Yao, M. Harvey, R.P. Harvey, N.L. Corry, B. Zhang, Y. Cox, C.D. |
Citation: | Science, 2023; 381(6659):799-804 |
Publisher: | American Association for the Advancement of Science (AAAS) |
Issue Date: | 2023 |
ISSN: | 0036-8075 1095-9203 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Myogenic Regulatory Factors |
Rights: | © 2023 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www. science.org/about/science-licenses-journal-article-reuse |
DOI: | 10.1126/science.adh8190 |
Grant ID: | http://purl.org/au-research/grants/arc/FT220100159 http://purl.org/au-research/grants/nhmrc/2021260 http://purl.org/au-research/grants/arc/DP200100860 |
Published version: | https://www.science.org/doi/10.1126/science.adh8190 |
Appears in Collections: | Research Outputs |
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