TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction

Xiaoxue Zhang; Jichen Shao; Caixue Wang; Chao Liu; Han Hao; Xinmeng Li; Yating An; Jinsha He; Weixin Zhao; Yiwen Zhao; Youzhen Kong; Zhanfeng Jia; Shaopo Wan; Yi Yuan; Huiran Zhang; Hailin Zhang; Xiaona Du

Cell Reports (Apr 2024)

TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction

Xiaoxue Zhang,
Jichen Shao,
Caixue Wang,
Chao Liu,
Han Hao,
Xinmeng Li,
Yating An,
Jinsha He,
Weixin Zhao,
Yiwen Zhao,
Youzhen Kong,
Zhanfeng Jia,
Shaopo Wan,
Yi Yuan,
Huiran Zhang,
Hailin Zhang,
Xiaona Du

Affiliations

Xiaoxue Zhang: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Jichen Shao: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Caixue Wang: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China; The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Chao Liu: Department of Animal Care, The Key Laboratory of Experimental Animal, Hebei Medical University, Shijiazhuang, Hebei, China
Han Hao: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Xinmeng Li: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Yating An: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Jinsha He: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Weixin Zhao: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Yiwen Zhao: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Youzhen Kong: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Zhanfeng Jia: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Shaopo Wan: Institute of Electrical Engineering, Yanshan University, Qinhuangdao, Hebei, China
Yi Yuan: Institute of Electrical Engineering, Yanshan University, Qinhuangdao, Hebei, China
Huiran Zhang: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Hailin Zhang: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
Xiaona Du: Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China; Corresponding author

Journal volume & issue: Vol. 43, no. 4
p. 114014

Abstract

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Summary: The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal β-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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