Abstract
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.
Highlights
Mechanosensitive ion channels (MSCs) open in response to mechanical forces (Guharay and Sachs, 1984; Guharay and Sachs, 1985; Kung, 2005; Sachs, 2010)
We sought to reproduce the mechanically evoked currents reported when TACAN is expressed in cells (Beaulieu-L aroche et al, 2020)
Purified TACAN protein reconstituted into giant unilamellar vesicles (GUVs) of soy L-α-phosphatidylcholine did not yield pressure-activated channels in membrane patches isolated from the GUVs (Figure 1E)
Summary
Mechanosensitive ion channels (MSCs) open in response to mechanical forces (Guharay and Sachs, 1984; Guharay and Sachs, 1985; Kung, 2005; Sachs, 2010). Ions flow across the cell membrane, triggering subsequent biochemical processes that represent a cellular response to the applied mechanical force. This coupling of transmembrane (TM) ion flow to mechanical forces underlies some forms of osmoregulation, cell and organ growth, blood pressure regulation, touch, and hearing (Chalfie, 2009; Coste et al, 2010; Pan et al, 2013; Peyronnet et al, 2012; Woo et al, 2015). A new MSC in mammals called TACAN was reported and proposed to mediate mechanical pain (Beaulieu-Laroche et al, 2020). As our laboratory studies the biophysical mechanisms by which MSCs transduce mechanical forces and conduct ions across membranes, we were intrigued by TACAN’s potential role as an MSC and set out to examine this function and report our findings here
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