Select autosomal dominant DFNA11 deafness variants activate Myo7A targeting in epithelial cells

Year: 2025

Type: article

Abstract: Myosin-7A (Myo7A) is a motor protein crucial for the organization and function of stereocilia, specialized actin-rich protrusions on the surface of inner ear hair cells that mediate hearing. Variants in Myo7A cause several forms of genetic hearing loss, including autosomal dominant DFNA11 deafness. Despite its importance, the structural elements that control Myo7A within cells are not well understood. In this study, we used cultured kidney epithelial cells to screen for mutations that activate the motor-dependent targeting of Myo7A to the tips of apical microvilli on these cells. Our findings reveal that the targeting of Myo7A is regulated by specific IQ motifs within its lever arm and that this regulation can function at least partially independent of its tail sequence. Importantly, we demonstrate that many of the DFNA11 deafness variants reported in patients activate Myo7A targeting, providing a potential explanation for the autosomal dominant genetics of this form of deafness.

Source: Journal of Cell Science

DOI: 10.1242/jcs.263982

Institutions: University of Toledo, Indiana University Indianapolis

Language: English

Topic: Hearing, Cochlea, Tinnitus, Genetics

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: University of Toledo, National Institutes of Health, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences

Awards: G2871733811, Molecular basis of apical protrusion organization and function in specialized epithelia, CDHR5 tumor suppressor function in the intestine, Cytoskeletal stability in stereocilia maintenance

OpenAlex ID: W4408672705