Recombinant Mouse Transmembrane channel-like protein 1 (Tmc1) Protein

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)

Subcellular Location

Cell membrane (Multi-pass membrane protein)

Disease Association

[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)]

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

Subunit

Forms the MET channel composed of TMC dimer (TMC1 or TMC2), TMIE, TOMT, CIB (CIB2 or CIB3), LHFPL5 and PCDH15 (PubMed:25114259, PubMed:28504928, PubMed:28534737, PubMed:28663585, PubMed:30138589, PubMed:34089643). Interacts with PIEZO1 and PIEZO2; the interaction may be part of the MET complex (PubMed:38228630). The interaction of TMC1 and TMC2 with TOMT is required for the transportation of TMC1/2 into the stereocilia of hair cells (PubMed:25114259, PubMed:28504928). Interacts (via N-terminus) with both isoforms CD1 and CD3 of PCDH15 (PubMed:25114259). Can form a heterodimer with TMC2, TMC5 or TMC7 (PubMed:30138589)

• Kurima K. et al. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. — Nat. Genet. (2002)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Keresztes G. et al. TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins. — BMC Genomics (2003)
• Pan B. et al. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. — Neuron (2013)
• Maeda R. et al. Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. — Proc. Natl. Acad. Sci. U.S.A. (2014)
• Cunningham C.L. et al. The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells. — Elife (2017)
• Erickson T. et al. Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt). — Elife (2017)
• Giese A.P.J. et al. CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells. — Nat. Commun. (2017)