{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:16:19Z","timestamp":1792278979590,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170694"],"award-info":[{"award-number":["32170694"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021ZD0203303"],"award-info":[{"award-number":["2021ZD0203303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024YFC2511100\/2024YFC2511104"],"award-info":[{"award-number":["2024YFC2511100\/2024YFC2511104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"The STI2030-Major Projects","doi-asserted-by":"publisher","award":["32170694"],"award-info":[{"award-number":["32170694"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"The STI2030-Major Projects","doi-asserted-by":"publisher","award":["2021ZD0203303"],"award-info":[{"award-number":["2021ZD0203303"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"The STI2030-Major Projects","doi-asserted-by":"publisher","award":["2024YFC2511100\/2024YFC2511104"],"award-info":[{"award-number":["2024YFC2511100\/2024YFC2511104"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"The STI2030-Major Projects","doi-asserted-by":"publisher","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Key R&amp;D Program of China","award":["32170694"],"award-info":[{"award-number":["32170694"]}]},{"name":"The National Key R&amp;D Program of China","award":["2021ZD0203303"],"award-info":[{"award-number":["2021ZD0203303"]}]},{"name":"The National Key R&amp;D Program of China","award":["2024YFC2511100\/2024YFC2511104"],"award-info":[{"award-number":["2024YFC2511100\/2024YFC2511104"]}]},{"name":"The National Key R&amp;D Program of China","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["32170694"],"award-info":[{"award-number":["32170694"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2021ZD0203303"],"award-info":[{"award-number":["2021ZD0203303"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2024YFC2511100\/2024YFC2511104"],"award-info":[{"award-number":["2024YFC2511100\/2024YFC2511104"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transmembrane channel-like (TMC) proteins are essential for hearing and balance; however, the molecular mechanisms that regulate their proper folding and membrane targeting remain poorly understood. Here, we establish Caenorhabditis elegans as a genetically tractable model to dissect TMC-1 trafficking by combining CRISPR knock-in strains, super-resolution microscopy, and genome-wide forward genetic screening. We show that TMC-1 robustly localizes to the plasma membrane in both neurons and muscle cells and identify a conserved valine (V803) in transmembrane domain 9 (TM9) as critical for its biogenesis and trafficking. Structural analyses guided by AlphaMissense and AlphaFold uncover two evolutionarily conserved functional hotspots, one in the extracellular loop adjacent to TM9 and the other in the TMC signature motif, which are interconnected by an evolutionarily conserved disulfide bond. Disrupting this bond in worm TMC-1 abolishes its cell-surface localization and destabilizes the mechanotransduction channel complex. Together, these findings provide a structural framework for interpreting deafness-causing mutations in human TMC1 and highlight disulfide-bond-linked hotspots as key molecular determinants of TMC protein biogenesis and trafficking.<\/jats:p>","DOI":"10.3390\/ijms26136356","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:45:08Z","timestamp":1751366708000},"page":"6356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Determinants of TMC Protein Biogenesis and Trafficking"],"prefix":"10.3390","volume":"26","author":[{"given":"Dedong","family":"Shao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinru","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7246-0205","authenticated-orcid":false,"given":"Xiaozhi","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilai","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai 200031, China"},{"name":"Institutes of Biomedical Science, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhui","family":"Qu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai 200031, China"},{"name":"Institutes of Biomedical Science, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Department of Systems Biology for Medicine, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-8897","authenticated-orcid":false,"given":"Yi-Quan","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1073\/pnas.74.6.2407","article-title":"Sensitivity, polarity, and conductance change in the response of vertebrate hair cells to controlled mechanical stimuli","volume":"74","author":"Hudspeth","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0006-3495(79)85267-4","article-title":"Response latency of vertebrate hair cells","volume":"26","author":"Corey","year":"1979","journal-title":"Biophys. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/281675a0","article-title":"Ionic basis of the receptor potential in a vertebrate hair cell","volume":"281","author":"Corey","year":"1979","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1172\/JCI60405","article-title":"Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes","volume":"121","author":"Kawashima","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.neuron.2013.06.019","article-title":"TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear","volume":"79","author":"Pan","year":"2013","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.neuron.2018.07.033","article-title":"TMC1 Forms the Pore of Mechanosensory Transduction Channels in Vertebrate Inner Ear Hair Cells","volume":"99","author":"Pan","year":"2018","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.neuron.2019.10.017","article-title":"TMC1 and TMC2 Proteins Are Pore-Forming Subunits of Mechanosensitive Ion Channels","volume":"105","author":"Jia","year":"2020","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41586-022-05314-8","article-title":"Structures of the TMC-1 complex illuminate mechanosensory transduction","volume":"610","author":"Jeong","year":"2022","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ng842","article-title":"Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function","volume":"30","author":"Kurima","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ng848","article-title":"Beethoven, a mouse model for dominant, progressive hearing loss DFNA36","volume":"30","author":"Vreugde","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31278","DOI":"10.1073\/pnas.2010782117","article-title":"Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis","volume":"117","author":"Boucher","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature25164","article-title":"Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents","volume":"553","author":"Gao","year":"2018","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41467-018-08264-w","article-title":"Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders","volume":"10","author":"Pan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yeh, W.H., Shubina-Oleinik, O., Levy, J.M., Pan, B., Newby, G.A., Wornow, M., Burt, R., Chen, J.C., Holt, J.R., and Liu, D.R. (2020). In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aay9101"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.ymthe.2020.11.016","article-title":"Single and Dual Vector Gene Therapy with AAV9-PHP.B Rescues Hearing in Tmc1 Mutant Mice","volume":"29","author":"Wu","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zheng, Z., Li, G., Cui, C., Wang, F., Wang, X., Xu, Z., Guo, H., Chen, Y., Tang, H., and Wang, D. (2022). Preventing autosomal-dominant hearing loss in Bth mice with CRISPR\/CasRx-based RNA editing. Signal Transduct. Target. Ther., 7.","DOI":"10.1038\/s41392-022-00893-4"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29894","DOI":"10.1073\/pnas.2011147117","article-title":"Deafness mutation D572N of TMC1 destabilizes TMC1 expression by disrupting LHFPL5 binding","volume":"117","author":"Yu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.1523\/JNEUROSCI.2537-20.2021","article-title":"New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells","volume":"41","author":"Beurg","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Akyuz, N., Karavitaki, K.D., Pan, B., Tamvakologos, P.I., Brock, K.P., Li, Y., Marks, D.S., and Corey, D.P. (2022). Mechanical gating of the auditory transduction channel TMC1 involves the fourth and sixth transmembrane helices. Sci. Adv., 8.","DOI":"10.1126\/sciadv.abo1126"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ballesteros, A., and Swartz, K.J. (2022). Regulation of membrane homeostasis by TMC1 mechanoelectrical transduction channels is essential for hearing. Sci. Adv., 8.","DOI":"10.1126\/sciadv.abm5550"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fettiplace, R., Furness, D.N., and Beurg, M. (2022). The conductance and organization of the TMC1-containing mechanotransducer channel complex in auditory hair cells. Proc. Natl. Acad. Sci. USA, 119.","DOI":"10.1073\/pnas.2210849119"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Beurg, M., Schwalbach, E.T., and Fettiplace, R. (2024). LHFPL5 is a key element in force transmission from the tip link to the hair cell mechanotransducer channel. Proc. Natl. Acad. Sci. USA, 121.","DOI":"10.1073\/pnas.2318270121"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.neuron.2024.11.009","article-title":"Human TMC1 and TMC2 are mechanically gated ion channels","volume":"113","author":"Fu","year":"2025","journal-title":"Neuron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41422-025-01075-x","article-title":"A force-sensitive adhesion GPCR is required for equilibrioception","volume":"35","author":"Yang","year":"2025","journal-title":"Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, Y., Li, Y., Liu, Y., Sun, J., Feng, W., Chen, Y., Tian, Y., Lei, T., and Huang, P. (2025). Ectopic mouse TMC1 and TMC2 alone form mechanosensitive channels that are potently modulated by TMIE. Proc. Natl. Acad. Sci. USA, 122.","DOI":"10.1073\/pnas.2403141122"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neuron.2020.03.026","article-title":"Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels","volume":"107","author":"Tang","year":"2020","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.celrep.2015.07.058","article-title":"TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia","volume":"12","author":"Kurima","year":"2015","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mahendrasingam, S., and Furness, D.N. (2019). Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37563-x"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, P., Miller, K.K., He, E., Dhawan, S.S., Cunningham, C.L., and Grillet, N. (2024). LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission. Nat. Commun., 15.","DOI":"10.1038\/s41467-024-51850-4"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Clark, S., Jeong, H., Posert, R., Goehring, A., and Gouaux, E. (2024). The structure of the Caenorhabditis elegans TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction. Proc. Natl. Acad. Sci. USA, 121.","DOI":"10.1073\/pnas.2314096121"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1016\/j.cell.2021.06.023","article-title":"Molecular topography of an entire nervous system","volume":"184","author":"Taylor","year":"2021","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cheng, J., Novati, G., Pan, J., Bycroft, C., Zemgulyte, A., Applebaum, T., Pritzel, A., Wong, L.H., Zielinski, M., and Sargeant, T. (2023). Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science, 381.","DOI":"10.1126\/science.adg7492"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Santos, R.L., Wajid, M., Khan, M.N., McArthur, N., Pham, T.L., Bhatti, A., Lee, K., Irshad, S., Mir, A., and Yan, K. (2005). Novel sequence variants in the TMC1 gene in Pakistani families with autosomal recessive hearing impairment. Hum. Mutat., 26.","DOI":"10.1002\/humu.9374"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1399-0004.2007.00895.x","article-title":"Identities, frequencies and origins of TMC1 mutations causing DFNB7\/B11 deafness in Pakistan","volume":"72","author":"Kitajiri","year":"2007","journal-title":"Clin. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijporl.2019.05.023","article-title":"Next-generation sequencing reveals a novel pathological mutation in the TMC1 gene causing autosomal recessive non-syndromic hearing loss in an Iranian kindred","volume":"124","author":"Sadeghian","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zardadi, S., Razmara, E., Asgaritarghi, G., Jafarinia, E., Bitarafan, F., Rayat, S., Almadani, N., Morovvati, S., and Garshasbi, M. (2020). Novel homozygous variants in the TMC1 and CDH23 genes cause autosomal recessive nonsyndromic hearing loss. Mol. Genet. Genom. Med., 8.","DOI":"10.1002\/mgg3.1550"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00439-023-02559-9","article-title":"Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome","volume":"142","author":"Tollefson","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng1044","article-title":"Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis","volume":"32","author":"Ramoz","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1083\/jcb.200311055","article-title":"Oxidative protein folding in eukaryotes: Mechanisms and consequences","volume":"164","author":"Tu","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1091\/mbc.e12-02-0102","article-title":"Vitamin K epoxide reductase contributes to protein disulfide formation and redox homeostasis within the endoplasmic reticulum","volume":"23","author":"Rutkevich","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ushioda, R., and Nagata, K. (2019). Redox-Mediated Regulatory Mechanisms of Endoplasmic Reticulum Homeostasis. Cold Spring Harb. Perspect. Biol., 11.","DOI":"10.1101\/cshperspect.a033910"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tibs.2022.06.011","article-title":"Oxidative protein folding fidelity and redoxtasis in the endoplasmic reticulum","volume":"48","author":"Wang","year":"2023","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ceb.2010.10.012","article-title":"Disulfide bonds in ER protein folding and homeostasis","volume":"23","author":"Feige","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.tem.2003.09.007","article-title":"Activation of G-protein-coupled receptors: A common molecular mechanism","volume":"14","author":"Karnik","year":"2003","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1210\/er.2013-1121","article-title":"Chaperoning G protein-coupled receptors: From cell biology to therapeutics","volume":"35","author":"Tao","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1073\/pnas.96.5.1932","article-title":"Structure and function in rhodopsin: Further elucidation of the role of the intradiscal cysteines, Cys-110, -185, and -187, in rhodopsin folding and function","volume":"96","author":"Hwa","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17464","DOI":"10.1074\/jbc.RA118.005624","article-title":"Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells","volume":"293","author":"Joseph","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fujii, S., Ushioda, R., and Nagata, K. (2023). Redox states in the endoplasmic reticulum directly regulate the activity of calcium channel, inositol 1,4,5-trisphosphate receptors. Proc. Natl. Acad. Sci. USA, 120.","DOI":"10.1073\/pnas.2216857120"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1091\/mbc.10.7.2209","article-title":"BiP and immunoglobulin light chain cooperate to control the folding of heavy chain and ensure the fidelity of immunoglobulin assembly","volume":"10","author":"Lee","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1091\/mbc.e02-05-0311","article-title":"A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins","volume":"13","author":"Meunier","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.molcel.2009.04.028","article-title":"An unfolded CH1 domain controls the assembly and secretion of IgG antibodies","volume":"34","author":"Feige","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1091\/mbc.10.8.2573","article-title":"ERp57 functions as a subunit of specific complexes formed with the ER lectins calreticulin and calnexin","volume":"10","author":"Oliver","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6288","DOI":"10.1093\/emboj\/20.22.6288","article-title":"Manipulation of oxidative protein folding and PDI redox state in mammalian cells","volume":"20","author":"Mezghrani","year":"2001","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7135","DOI":"10.1074\/jbc.M109.082545","article-title":"Novel thioredoxin-related transmembrane protein TMX4 has reductase activity","volume":"285","author":"Sugiura","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1159293","article-title":"ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER","volume":"321","author":"Ushioda","year":"2008","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1534\/genetics.110.119230","article-title":"A strategy for direct mapping and identification of mutations by whole-genome sequencing","volume":"186","author":"Zuryn","year":"2010","journal-title":"Genetics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1534\/genetics.118.301532","article-title":"Robust Genome Editing with Short Single-Stranded and Long, Partial-ly Single-Stranded DNA Donors in Caenorhabditis elegans","volume":"210","author":"Dokshin","year":"2018","journal-title":"Genetics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1046-2023(03)00050-1","article-title":"Genome-wide RNAi screening in Caenorhabditis elegans","volume":"30","author":"Kamath","year":"2003","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:37Z","timestamp":1760032957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":60,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136356"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136356","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}