| Structural highlights
Disease
WHRN_HUMAN Defects in DFNB31 are the cause of deafness autosomal recessive type 31 (DFNB31) [MIM:607084. DFNB31 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[1] [2] [3] Defects in DFNB31 are the cause of Usher syndrome type 2D (USH2D) [MIM:611383. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses.
Function
WHRN_HUMAN Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear (By similarity).
Publication Abstract from PubMed
Stereocilia, the mechanosensory organelles on the apical surface of hair cells, are necessary to detect sound and carry out mechano-electrical transduction. An electron-dense matrix is located at the distal tips of stereocilia and plays crucial roles in the regulation of stereocilia morphology. Mutations of the components in this tip complex density (TCD) have been associated with profound deafness. However, the mechanism underlying the formation of the TCD is largely unknown. Here, we discover that the specific multivalent interactions among the Whirlin-myosin 15 (Myo15)-Eps8 complex lead to the formation of the TCD-like condensates through liquid-liquid phase separation. The reconstituted TCD-like condensates effectively promote actin bundling. A deafness-associated mutation of Myo15 interferes with the condensates formation and consequently impairs actin bundling. Therefore, our study not only suggests that the TCD in hair cell stereocilia may form via phase separation but it also provides important clues for the possible mechanism underlying hearing loss.
Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex.,Lin L, Shi Y, Wang M, Wang C, Lu Q, Zhu J, Zhang R Cell Rep. 2021 Feb 23;34(8):108770. doi: 10.1016/j.celrep.2021.108770. PMID:33626355[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mustapha M, Chouery E, Chardenoux S, Naboulsi M, Paronnaud J, Lemainque A, Megarbane A, Loiselet J, Weil D, Lathrop M, Petit C. DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34. Eur J Hum Genet. 2002 Mar;10(3):210-2. PMID:11973626 doi:10.1038/sj.ejhg.5200780
- ↑ Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet. 2003 Aug;34(4):421-8. PMID:12833159 doi:10.1038/ng1208
- ↑ Tlili A, Charfedine I, Lahmar I, Benzina Z, Mohamed BA, Weil D, Idriss N, Drira M, Masmoudi S, Ayadi H. Identification of a novel frameshift mutation in the DFNB31/WHRN gene in a Tunisian consanguineous family with hereditary non-syndromic recessive hearing loss. Hum Mutat. 2005 May;25(5):503. PMID:15841483 doi:10.1002/humu.9333
- ↑ Lin L, Shi Y, Wang M, Wang C, Lu Q, Zhu J, Zhang R. Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex. Cell Rep. 2021 Feb 23;34(8):108770. PMID:33626355 doi:10.1016/j.celrep.2021.108770
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