The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells

eLife

Sarah Harkins-Perry¹  Bo Zhao²  Amanda Lauer³  Kat Schrode³  Aria Jafari⁴  Ulrich Müller⁵  Christopher L Cunningham⁵  Zizhen Wu⁵ 

[1] Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, United States;Department of Otolaryngology Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, United States;Department of Otolaryngology, Johns Hopkins University, Baltimore, United States;Department of Surgery, University of California, San Diego, San Diego, United States;The Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United States;

关键词: hair cell;    mechanotransduction;    hearing;    Tomt;    stereocilia;   

DOI  :  10.7554/eLife.24318

来源: DOAJ

【 摘 要 】

Hair cells of the cochlea are mechanosensors for the perception of sound. Mutations in the LRTOMT gene, which encodes a protein with homology to the catecholamine methyltransferase COMT that is linked to schizophrenia, cause deafness. Here, we show that Tomt/Comt2, the murine ortholog of LRTOMT, has an unexpected function in the regulation of mechanotransduction by hair cells. The role of mTOMT in hair cells is independent of mTOMT methyltransferase function and mCOMT cannot substitute for mTOMT function. Instead, mTOMT binds to putative components of the mechanotransduction channel in hair cells and is essential for the transport of some of these components into the mechanically sensitive stereocilia of hair cells. Our studies thus suggest functional diversification between mCOMT and mTOMT, where mTOMT is critical for the assembly of the mechanotransduction machinery of hair cells. Defects in this process are likely mechanistically linked to deafness caused by mutations in LRTOMT/Tomt.

【 授权许可】

Unknown