Analysis of the mechanosensor channel functionality of TACAN

eLife

Paul Dominic B Olinares¹  Brian T Chait¹  Yiming Niu²  George Vaisey³  Roderick MacKinnon³  Xiao Tao³  Hanan Alwaseem⁴ 

[1] Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, United States;Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States;Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States;Howard Hughes Medical Institute, New York, United States;Proteomics Resource Center, Rockefeller University, New York, United States;

关键词: mechanosensation;    lipid metabolism;    coenzyme A;    ion channel;    Human;    Mouse;   

DOI  :  10.7554/eLife.71188

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Mechanosensitive ion channels mediate transmembrane ion currents activated by mechanical forces. A mechanosensitive ion channel called TACAN was recently reported. We began to study TACAN with the intent to understand how it senses mechanical forces and functions as an ion channel. Using cellular patch-recording methods, we failed to identify mechanosensitive ion channel activity. Using membrane reconstitution methods, we found that TACAN, at high protein concentrations, produces heterogeneous conduction levels that are not mechanosensitive and are most consistent with disruptions of the lipid bilayer. We determined the structure of TACAN using single-particle cryo-electron microscopy and observed that it is a symmetrical dimeric transmembrane protein. Each protomer contains an intracellular-facing cleft with a coenzyme A cofactor, confirmed by mass spectrometry. The TACAN protomer is related in three-dimensional structure to a fatty acid elongase, ELOVL7. Whilst its physiological function remains unclear, we anticipate that TACAN is not a mechanosensitive ion channel.

【 授权许可】

CC BY