1.A.82.1.1
Mechanotransduction channel complex of cochlear hair cells TMHS/LHFPL5 is encoded by the Lhfpl5 gene.  The complex contains several proteins:  the tetraspan membrane protein of hair cell stereocilia, (TMHS protein) or Lipoma HMGIC fusion partner-like 5 protein (LHFPL5) (Fettiplace 2016), the Protocadherin-15 protein, PCDH15, and the Tmc1 and Tmc2 proteins (TC# 1.A.17) (Xiong et al. 2012).  TMHS and PCDH15 interact directly with Tmc1 and Tmc2, and these interactions are required for mechanotransduction (Maeda et al. 2014; Beurg et al. 2015). A primary function of Tmc1 may be calcium transport (Beurg et al. 2015).  Hair cells express two molecularly and functionally distinct mechanotransduction channels with different subcellular distributions. One is activated by sound and is responsible for sensory transduction. This sensory transduction channel is expressed in hair cell stereocilia, and its activity is affected by mutations in the genes encoding the transmembrane proteins TMHS (this family), TMIE (TC family 8.A.116), TMC1 and TMC2 (family 1.A.17.4) (Wu et al. 2016). Thus, these 4 proteins may all be parts of a single channel complex.  The other channel is the Piezo2 channel (TC# 1.A.75.1.2). TMHS is 68% identical to the human LHFPL3 protein (Q86UP9), and 62% identical to the human LHFPL4 protein (Q7Z7J7). The structure of protocadherin 15 with the tetraspan, LHFP5, has been determined (Ge et al. 2018). Deafness mutation D572N of TMC1 destabilizes TMC1 expression by disrupting LHFPL5 binding (Yu et al. 2020).