Ask about this productRelated genes to: TMC2 Blocking Peptide
- Gene:
- TMC2 NIH gene
- Name:
- transmembrane channel like 2
- Previous symbol:
- C20orf145
- Synonyms:
- dJ686C3.3
- Chromosome:
- 20p13
- Locus Type:
- gene with protein product
- Date approved:
- 2001-10-08
- Date modifiied:
- 2015-11-12
Related products to: TMC2 Blocking Peptide
Related articles to: TMC2 Blocking Peptide
- This literature review explores in depth the molecular pharmacology and signaling networks in the cochlear microenvironment, a key organ for hearing. The cochlea converts sound vibrations into electrical signals using hair cells and a complex network of receptors and ion channels. Sensorineural hearing loss affects more than 1.5 billion people and is irreversible in adult mammals, underscoring the importance of understanding the molecular mechanisms underlying this condition to develop new therapies. Auditory transduction depends on mechanosensitive channels (TMC1/TMC2) and ionotropic and metabotropic receptors, such as those for glutamate, acetylcholine, dopamine, adenosine, and ATP. These regulate neurotransmission and homeostasis, protecting against damage from noise or ototoxic drugs. Endolymphatic homeostasis, essential for the endocochlear potential, is maintained by the stria vascularis and the spiral ligament, regulated by nuclear and membrane receptors. This review highlights promising pharmacological therapies, such as adenosine A1 agonists (ADAC, CCPA) and P2X/P2Y receptor antagonists, which protect hair cells after noise exposure. Agents such as muscimol (GABA-A) and piribedil (D2/D3) regulate neuronal excitability and prevent excitotoxicity. Glucocorticoids (such as dexamethasone) induce the expression of anti-inflammatory and antioxidant proteins, thereby enhancing cellular resilience. The aim of this review is to characterize the receptors, channels, and signaling pathways in the cochlea, enabling the identification of therapeutic strategies to prevent and treat hearing loss. A thorough understanding of the molecular microenvironment is essential for advancing otoprotective and regenerative solutions that improve the quality of life for those with hearing disorders. - Source: PubMed
Publication date: 2026/07/15
Munoz FelipeGonzález-Candia AlejandroTerreros Gonzalo - The internal electron donor is a crucial component of modern Ziegler-Natta catalysts. In this manuscript, we investigated the adsorption behavior of dimethyl phthalate (DMP), dimethyl 2,3-dimethylsuccinate (DMS), and 2,2-dimethyl-1,3-dimethoxypropane (DMMP) on the multisite titanium active center model named TMC-2, as well as the coordination and insertion processes of isoprene using density functional theory (DFT). Among the models, the DMS chelating adsorption configuration (TMC-2*) exhibited the lowest reaction energy barrier (ΔG = 31.2 kcal/mol) and the highest stereoselectivity (ΔGstereo = 9.2 kcal/mol) during isoprene polymerization. In contrast, the adsorption of DMP and DMMP exerted only a marginal influence on both the geometric parameters of the active centers and the reaction energy barrier. In summary, the adsorption mode and type of internal electron donors significantly influence the coordination free energy and insertion energy barrier of isoprene. For the two insertion modes of isoprene, named re- and si- spatial configurations, the cis-1,4-re configuration presents the methyl substituents pointing to the right (clockwise when viewed down the C1-C4 axis), whereas the cis-1,4-si configuration presents them to the left (counterclockwise); this local chirality dictates which face can readily access the titanium center after donor adsorption. The reconfigured isoprene can spontaneously coordinate across all internal electron donor adsorption models, whereas the coordination process for the si configuration is strongly hindered. - Source: PubMed
Publication date: 2026/05/20
Sui KaiQingLiu JianChen JieZhou RunChuanHe AiHuaYang Xia - The transmembrane channel-like (TMC) gene family encodes membrane proteins required for hair cell mechanotransduction. While TMC1 and TMC2 are indispensable for mammalian hearing, the functions of other paralogs remain poorly defined. Using zebrafish, we examined nine TMC genes (tmc1, tmc2a, tmc2b, tmc3, tmc4, tmc5, tmc6a, tmc6b, and tmc8) through phylogenetic, transcriptomic, and spatiotemporal expression analyses. tmc1, tmc2a, and tmc2b were robustly expressed in hair cells of the otic vesicle and neuromasts, supporting their early roles in hair cell differentiation. tmc3 and tmc6a showed clear expression by in situ hybridization but were underrepresented in transcriptomic datasets. tmc4 and tmc5 were more broadly expressed, including vestibular hair cells and neuromasts from 72 to 96 h post-fertilization (hpf). Several TMC genes were also detected in non-sensory tissues, suggesting potential roles in other developmental processes. Together, this study provides the first comprehensive atlas of TMC gene expression during zebrafish embryogenesis and reveals divergent expression patterns among paralogs. - Source: PubMed
Publication date: 2026/04/22
Geng KaixiWang XunWang XinLiu DongQian Fuping - TMC1 and TMC2 are mechanosensory ion channels of the vertebrate inner ear that mediate hearing and balance. How these channels open in response to mechanical force remains unresolved. Through comparative analyses of TMCs across eukaryote species, we find that TMC1 and TMC2 arose in vertebrates by gene duplication and evolved elaborate extracellular loops. Structural models demonstrate that the loop between transmembrane domains 1 and 2 arches over the channel pore and lies near TMIE, an auxiliary protein essential for function. In mammals, this loop shows signatures of positive selection and contains multiple sites linked to hereditary deafness, consistent with TMC1's specialization for auditory function. Electrophysiological recordings from mouse Tmc1/Tmc2-null cochlear hair cells expressing TMC1 variants demonstrate that alterations within this loop affect channel activation, identifying it as a modulatory feature that has been refined through structural adaptation. - Source: PubMed
Publication date: 2026/03/25
Akyuz NurunisaScott Trey JLoeb CorenaPan BifengLi YaqiaoPhillips Charles BBellono Nicholas WCorey David P - Sensory hair cells convert sound-induced vibrations into electrical signals through a process called mechanoelectrical transduction (MET). While the protein components of the MET complex are well studied, increasing evidence indicates that MET channel properties are significantly modulated by the surrounding lipid bilayer. The asymmetric distribution of membrane lipids between the inner and outer membrane leaflets is well established to shape membrane mechanics. The recent discovery that the core MET components TMC1 and TMC2 also act as lipid scramblases suggests a direct role for membrane lipid asymmetry in the dynamic shaping of auditory transduction. Because scramblase activity of TMC1/2 disrupts lipid asymmetry, we hypothesized that an opposing flippase may be required to restore and maintain lipid asymmetry. Here, we identify the P4-ATPase ATP8B1 and its chaperone TMEM30B as selectively expressed in outer hair cells (OHCs), enriched in stereocilia, and upregulated following the onset of MET and hearing. Loss of either protein results in elevated auditory brainstem response (ABR) thresholds, phosphatidylserine (PS) externalization, and rapid hair-cell degeneration, demonstrating that lipid homeostasis is crucial for OHC survival. Together, these findings establish ATP8B1 and TMEM30B as key regulators of membrane lipid asymmetry in sensory hair cells and establish TMEM30B as a novel deafness gene. - Source: PubMed
Publication date: 2026/02/13
De Hoyos Henry NLi SihanIm Jun-SubLuz-Ricca AlyssaSzeto BetsyJonas RachelKim EmmaAmin NikhilShin Jung-Bum