Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2021 Aug 9

PMID 34366792

Citations 4

Authors

Chang Liu

Bo Zhao

Affiliations

Soon will be listed here.

Abstract

Mutations in human glutaredoxin domain-containing cysteine-rich protein 1 () and its paralog have been linked to hearing loss in humans. Although both GRXCR1 and GRXCR2 are required for the morphogenesis of stereocilia in cochlear hair cells, a fundamental question that remains unclear is whether GRXCR1 and GRXCR2 have similar functions in hair cells. Previously, we found that GRXCR2 is critical for the stereocilia morphogenesis by regulating taperin localization at the base of stereocilia. Reducing taperin expression level rescues the morphological defects of stereocilia and hearing loss in -deficient mice. So far, functions of GRXCR1 in mammalian hair cells are still unclear. -deficient hair cells have very thin stereocilia with less F-actin content inside, which is different from -deficient hair cells. In contrast to GRXCR2, which is concentrated at the base of stereocilia, GRXCR1 is diffusely distributed throughout the stereocilia. Notably, GRXCR1 interacts with GRXCR2. In -deficient hair cells, the expression level of GRXCR2 and taperin is reduced. Remarkably, different from that in -deficient mice, reducing taperin expression level does not rescue the morphological defects of stereocilia or hearing loss in -deficient mice. Thus, our findings suggest that GRXCR1 has different functions than GRXCR2 during the morphogenesis of stereocilia.

Citing Articles

A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment.

Yeo X, Kwon S, Rinai K, Lee S, Jung S, Park R Antioxidants (Basel). 2024; 13(5).

PMID: 38790703 PMC: 11118506. DOI: 10.3390/antiox13050598.

Genome-wide detection of positive and balancing signatures of selection shared by four domesticated rainbow trout populations (Oncorhynchus mykiss).

Paul K, Restoux G, Phocas F Genet Sel Evol. 2024; 56(1):13.

PMID: 38389056 PMC: 10882880. DOI: 10.1186/s12711-024-00884-9.

RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss.

Li J, Liu C, Muller U, Zhao B Dev Cell. 2022; 57(18):2204-2220.e6.

PMID: 36113482 PMC: 9529990. DOI: 10.1016/j.devcel.2022.08.011.

Collapsin Response Mediator Protein 1 (CRMP1) Is Required for High-Frequency Hearing.

Li J, Liu C, Zhao B Am J Pathol. 2022; 192(5):805-812.

PMID: 35181334 PMC: 9088201. DOI: 10.1016/j.ajpath.2022.01.011.

References

Zhao B, Wu Z, Muller U . Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. Elife. 2016; 5. PMC: 4898930. DOI: 10.7554/eLife.14222. View

Liu C, Luo N, Tung C, Perrin B, Zhao B . GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing. Cell Rep. 2018; 25(5):1268-1280.e4. PMC: 6317715. DOI: 10.1016/j.celrep.2018.09.063. View

Imtiaz A, Kohrman D, Naz S . A frameshift mutation in GRXCR2 causes recessively inherited hearing loss. Hum Mutat. 2014; 35(5):618-24. PMC: 4123198. DOI: 10.1002/humu.22545. View

Scheffer D, Shen J, Corey D, Chen Z . Gene Expression by Mouse Inner Ear Hair Cells during Development. J Neurosci. 2015; 35(16):6366-80. PMC: 4405555. DOI: 10.1523/JNEUROSCI.5126-14.2015. View

Avenarius M, Jung J, Askew C, Jones S, Hunker K, Azaiez H . Grxcr2 is required for stereocilia morphogenesis in the cochlea. PLoS One. 2018; 13(8):e0201713. PMC: 6114524. DOI: 10.1371/journal.pone.0201713. View

Gillespie P, Muller U . Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell. 2009; 139(1):33-44. PMC: 2888516. DOI: 10.1016/j.cell.2009.09.010. View

Mieyal J, Starke D, Gravina S, Dothey C, Chung J . Thioltransferase in human red blood cells: purification and properties. Biochemistry. 1991; 30(25):6088-97. DOI: 10.1021/bi00239a002. View

Blanco-Sanchez B, Clement A, Fierro Jr J, Stednitz S, Phillips J, Wegner J . Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins. Cell Rep. 2018; 25(5):1281-1291.e4. PMC: 6284068. DOI: 10.1016/j.celrep.2018.10.005. View

Schraders M, Lee K, Oostrik J, Huygen P, Ali G, Hoefsloot L . Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment. Am J Hum Genet. 2010; 86(2):138-47. PMC: 2820176. DOI: 10.1016/j.ajhg.2009.12.017. View

10.

Wonkam A, Lebeko K, Mowla S, Noubiap J, Chong M, Pare G . Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon. Mol Genet Genomic Med. 2021; 9(3):e1609. PMC: 8104159. DOI: 10.1002/mgg3.1609. View

11.

Senften M, Schwander M, Kazmierczak P, Lillo C, Shin J, Hasson T . Physical and functional interaction between protocadherin 15 and myosin VIIa in mechanosensory hair cells. J Neurosci. 2006; 26(7):2060-71. PMC: 2712835. DOI: 10.1523/JNEUROSCI.4251-05.2006. View

12.

Richardson G, de Monvel J, Petit C . How the genetics of deafness illuminates auditory physiology. Annu Rev Physiol. 2010; 73:311-34. DOI: 10.1146/annurev-physiol-012110-142228. View

13.

Whippo C, Khurana P, Davis P, DeBlasio S, DeSloover D, Staiger C . THRUMIN1 is a light-regulated actin-bundling protein involved in chloroplast motility. Curr Biol. 2010; 21(1):59-64. DOI: 10.1016/j.cub.2010.11.059. View

14.

Lefevre G, Michel V, Weil D, Lepelletier L, Bizard E, Wolfrum U . A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development. 2008; 135(8):1427-37. DOI: 10.1242/dev.012922. View

15.

Corns L, Johnson S, Roberts T, Ranatunga K, Hendry A, Ceriani F . Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation. Nat Commun. 2018; 9(1):4015. PMC: 6167318. DOI: 10.1038/s41467-018-06307-w. View

16.

Erven A, Skynner M, Okumura K, Takebayashi S, Brown S, Steel K . A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil. Eur J Neurosci. 2002; 16(8):1433-41. DOI: 10.1046/j.1460-9568.2002.02213.x. View

17.

Gladyshev V, Liu A, Novoselov S, Krysan K, Sun Q, Kryukov V . Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2. J Biol Chem. 2001; 276(32):30374-80. DOI: 10.1074/jbc.M100020200. View

18.

Beyer L, Odeh H, Probst F, LAMBERT E, Dolan D, Camper S . Hair cells in the inner ear of the pirouette and shaker 2 mutant mice. J Neurocytol. 2001; 29(4):227-40. DOI: 10.1023/a:1026515619443. View

19.

Odeh H, Hunker K, Belyantseva I, Azaiez H, Avenarius M, Zheng L . Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse. Am J Hum Genet. 2010; 86(2):148-60. PMC: 2820167. DOI: 10.1016/j.ajhg.2010.01.016. View

20.

Odeh H, Hagiwara N, Skynner M, Mitchem K, Beyer L, Allen N . Characterization of two transgene insertional mutations at pirouette, a mouse deafness locus. Audiol Neurootol. 2004; 9(5):303-14. DOI: 10.1159/000080701. View