Tmc1
Developmental stage
Expressed at low, constant levels in temporal bone from embryonic day 14 to day 1 after birth. Increases by 8 to 16-fold at day 5, 10 and 20 and continues to be expressed up to day 90.
Domain
TMC1 is structurally similar to TMEM16 channel and may include ten transmembrane (TM) domains with the ion-conducting pore placed between TM4 and TM7.
Function
Pore-forming subunit of the mechanotransducer (MET) non-selective cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system (PubMed:11850618, PubMed:23871232, PubMed:30138589, PubMed:36191207). The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, the tip-link PCDH15, and possibly the PIEZO subunits (PubMed:30138589, PubMed:36191207). MET channel is activated by tension in the tip-link extending from the side wall of one stereocilium to the tip of the adjacent shorter stereocilium, where the channel is located (PubMed:30138589, PubMed:36191207). TMC1 MET channel is highly permeable to calcium and likely transports monovalent cations (PubMed:23871232, PubMed:30138589, PubMed:36191207). Also involved in vestibular hair cells transduction current (PubMed:23871232).
Involvement in disease
Defects in Tmc1 are the cause of the dominant deaf mutant Beethoven (BTH). Heterozygotes show progressive hair-cell degeneration from day 20 onwards, leading to severe depletion of inner hair cells and scattered loss of outer hair cells, and progressive loss of the Preyer reflex from around day 30. Homozygotes show almost complete degeneration of inner hair cells, and little or no Preyer reflex at any age.
Defects in Tmc1 are the cause of recessive deaf mutant dn. The dn mutant shows profound deafness with degeneration of the organ of Corti, stria vascularis, and occasionally the saccular macula, starting at about 10 days after birth (PubMed:11850618).
Sequence Similarities
Belongs to the TMC family.
Tissue Specificity
Detected in cochlear inner and outer hair cells and in neurosensory epithelia of the vestibular end organs (PubMed:38228630). Also expressed in cortex, cerebellum, eye, colon, ovary and testis.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Localized to the stereocilia tips of the cochlear hair cells.
Alternative names
Bth, dn, Tmc1, Transmembrane channel-like protein 1, Beethoven protein, Deafness protein, Transmembrane cochlear-expressed protein 1