Cochlin Explained

Cochlin is a protein that in humans is encoded by the COCH gene.^{[1] [2]} It is an extracellular matrix (ECM) protein highly abundant in the cochlea and vestibule of the inner ear, constituting the major non-collagen component of the ECM of the inner ear.^{[3] [4]} The protein is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively.

Structure

Cochlin contains three protein domains: an N-terminal LCCL domain, and two copies of Von Willebrand factor type A domains.^[5]

Function

The gene is expressed in spindle-shaped cells located along nerve fibers between the auditory ganglion and sensory epithelium. These cells accompany neurites at the habenula perforata, the opening through which neurites extend to innervate hair cells. This and the pattern of expression of this gene in chicken inner ear paralleled the histologic findings of acidophilic deposits, consistent with mucopolysaccharide ground substance, in temporal bones from DFNA9 (autosomal dominant nonsyndromic sensorineural deafness 9) patients. Mutations that cause DFNA9 have been reported in this gene.

Cochlin has been identified in the trabecular meshwork (TM) of glaucoma patients, but not in healthy controls. The TM is a filter like area of tissue in the eye; cochlin may have a role in cell adhesion, mechanosensation, and modulation of the TM filter.^{[6] [7]}

It is also expressed in follicular dendritic cells in spleen and lymph nodes. Here, cochlin is cleaved by aggrecanases and secreted into blood circulation during inflammation, contributing to the antibacterial innate immune response.^[8]

References

Further reading

• Khetarpal U, Schuknecht HF, Gacek RR, Holmes LB . Autosomal dominant sensorineural hearing loss. Pedigrees, audiologic findings, and temporal bone findings in two kindreds . Archives of Otolaryngology–Head & Neck Surgery . 117 . 9 . 1032–42 . September 1991 . 1910721 . 10.1001/archotol.1991.01870210104022 .
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC . Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening . Genomics . 23 . 1 . 42–50 . September 1994 . 7829101 . 10.1006/geno.1994.1457 .
• Khetarpal U . Autosomal dominant sensorineural hearing loss. Further temporal bone findings . Archives of Otolaryngology–Head & Neck Surgery . 119 . 1 . 106–8 . January 1993 . 8417734 . 10.1001/archotol.1993.01880130108016 .
• Manolis EN, Yandavi N, Nadol JB, Eavey RD, McKenna M, Rosenbaum S, Khetarpal U, Halpin C, Merchant SN, Duyk GM, MacRae C, Seidman CE, Seidman JG . A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13 . Human Molecular Genetics . 5 . 7 . 1047–50 . July 1996 . 8817345 . 10.1093/hmg/5.7.1047 . free .
  • de Kok YJ, Bom SJ, Brunt TM, Kemperman MH, van Beusekom E, van der Velde-Visser SD, Robertson NG, Morton CC, Huygen PL, Verhagen WI, Brunner HG, Cremers CW, Cremers FP . A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects . Human Molecular Genetics . 8 . 2 . 361–6 . February 1999 . 9931344 . 10.1093/hmg/8.2.361 . free .
• Fransen E, Verstreken M, Verhagen WI, Wuyts FL, Huygen PL, D'Haese P, Robertson NG, Morton CC, McGuirt WT, Smith RJ, Declau F, Van de Heyning PH, Van Camp G . High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene . Human Molecular Genetics . 8 . 8 . 1425–9 . August 1999 . 10400989 . 10.1093/hmg/8.8.1425 . free .
• Kamarinos M, McGill J, Lynch M, Dahl H . Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families . Human Mutation . 17 . 4 . 351 . April 2001 . 11295836 . 10.1002/humu.37 . free .
• Boulassel MR, Tomasi JP, Deggouj N, Gersdorff M . COCH5B2 is a target antigen of anti-inner ear antibodies in autoimmune inner ear diseases . Otology & Neurotology . 22 . 5 . 614–8 . September 2001 . 11568667 . 10.1097/00129492-200109000-00009 . 37332746 .
• Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Bányai L, Patthy L, Otting G . NMR structure of the LCCL domain and implications for DFNA9 deafness disorder . The EMBO Journal . 20 . 19 . 5347–53 . October 2001 . 11574466 . 125649 . 10.1093/emboj/20.19.5347 .
• Robertson NG, Resendes BL, Lin JS, Lee C, Aster JC, Adams JC, Morton CC . Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9 . Human Molecular Genetics . 10 . 22 . 2493–500 . October 2001 . 11709536 . 10.1093/hmg/10.22.2493 . free .
• Robertson NG, Hamaker SA, Patriub V, Aster JC, Morton CC . Subcellular localisation, secretion, and post-translational processing of normal cochlin, and of mutants causing the sensorineural deafness and vestibular disorder, DFNA9 . Journal of Medical Genetics . 40 . 7 . 479–86 . July 2003 . 12843317 . 1735525 . 10.1136/jmg.40.7.479 .
• Grabski R, Szul T, Sasaki T, Timpl R, Mayne R, Hicks B, Sztul E . Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin . Human Genetics . 113 . 5 . 406–16 . October 2003 . 12928864 . 10.1007/s00439-003-0992-7 . 19560837 .
• Lemaire FX, Feenstra L, Huygen PL, Fransen E, Devriendt K, Van Camp G, Vantrappen G, Cremers CW, Wackym PA, Koss JC . Progressive late-onset sensorineural hearing loss and vestibular impairment with vertigo (DFNA9/COCH): longitudinal analyses in a belgian family . Otology & Neurotology . 24 . 5 . 743–8 . September 2003 . 14501450 . 10.1097/00129492-200309000-00009 . 42011530 .
• Usami S, Takahashi K, Yuge I, Ohtsuka A, Namba A, Abe S, Fransen E, Patthy L, Otting G, Van Camp G . Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease . European Journal of Human Genetics . 11 . 10 . 744–8 . October 2003 . 14512963 . 10.1038/sj.ejhg.5201043 . 23054678 .
• Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A . The human plasma proteome: a nonredundant list developed by combination of four separate sources . Molecular & Cellular Proteomics . 3 . 4 . 311–26 . April 2004 . 14718574 . 10.1074/mcp.M300127-MCP200 . free .

Notes and References

1. Robertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, Nadol JB, Miyamoto RT, Linthicum FH, Lubianca Neto JF, Hudspeth AJ, Seidman CE, Morton CC, Seidman JG . Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction . Nature Genetics . 20 . 3 . 299–303 . November 1998 . 9806553 . 10.1038/3118 . 16350815 .
2. Web site: Entrez Gene: COCH coagulation factor C homolog, cochlin (Limulus polyphemus).
3. Robertson NG, Skvorak AB, Yin Y, Weremowicz S, Johnson KR, Kovatch KA, Battey JF, Bieber FR, Morton CC . Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9 . Genomics . 46 . 3 . 345–54 . December 1997 . 9441737 . 10.1006/geno.1997.5067 .
4. Ikezono T, Omori A, Ichinose S, Pawankar R, Watanabe A, Yagi T . Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1535 . 3 . 258–65 . March 2001 . 11278165 . 10.1016/s0925-4439(00)00101-0. free .
5. Web site: Cochlin (O43405) . InterPro < EMBL-EBI.
6. Goel M, Sienkiewicz AE, Picciani R, Lee RK, Bhattacharya SK . Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility . PLOS ONE . 6 . 8 . e23070 . 2011 . 21886777 . 10.1371/journal.pone.0023070 . 3160293 . 2011PLoSO...623070G . free .
7. Picciani R, Desai K, Guduric-Fuchs J, Cogliati T, Morton CC, Bhattacharya SK . Cochlin in the eye: functional implications . Progress in Retinal and Eye Research . 26 . 5 . 453–69 . September 2007 . 17662637 . 10.1016/j.preteyeres.2007.06.002 . 2064858 .
8. Py BF, Gonzalez SF, Long K, Kim MS, Kim YA, Zhu H, Yao J, Degauque N, Villet R, Ymele-Leki P, Gadjeva M, Pier GB, Carroll MC, Yuan J . Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity . Immunity . 38 . 5 . 1063–72 . May 2013 . 23684986 . 10.1016/j.immuni.2013.01.015 . 3758559 .