Abstract
The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1-/- mice) were generated to investigate LKB1 function in the inner ear. Tests of auditory brainstem response and distortion product otoacoustic emissions revealed significant decreases in the hearing sensitivities of the Atoh1-LKB1-/- mice. In Atoh1-LKB1-/- mice, malformations of hair cell stereocilliary bundles were present as early as postnatal day 1 (P1), a time long before the maturation of the hair cell bundles. In addition, we also observed outer hair cell (OHC) loss starting at P14. The impaired stereocilliary bundles occurred long before the presence of hair cell loss. Stereociliary cytoskeletal structure depends on the core actin-based cytoskeleton and several actin-binding proteins. By Western blot, we examined actin-binding proteins, specifically ERM (ezrin/radixin/moesin) proteins involved in the regulation of the actin cytoskeleton of hair cell stereocilia. Our results revealed that the phosphorylation of ERM proteins (pERM) was significantly decreased in mutant mice. Thus, we propose that the decreased pERM may be a key factor for the impaired stereocillia function, and the damaged stereocillia may induce hair cell loss and hearing impairments. Taken together, our data indicates that LKB1 is required for the development and maintenance of stereocilia in the inner ear.
Highlights
Sound transduction initiates in the external auditory canal and leads to the vibration of the tympanic membrane or the eardrum
Whole mount immunostaining was used to examine the expression pattern of liver kinase B1 (LKB1) in the cochlea hair cells, and the results showed a high level of expression in both the nuclei and cytoplasm in the wild-type mice (WT) mice (Fig 2A)
Using cochlear whole mounts labeled with phalloidin, we subsequently examined the morphology of stereociliary bundles of hair cells in Atoh1-LKB1-/- mice at p1, p7 and p21 (Fig 4C)
Summary
Sound transduction initiates in the external auditory canal and leads to the vibration of the tympanic membrane or the eardrum. Hair cells contain hairlike stereocilia that transmits sound signals based on the movement of the tectorial membrane, leading to the release of the neurotransmitter glutamate. This cascade results in activation of afferent neurons collectively known as the cochlear branch of the vestibulocochlear nerve that feeds into the auditory cortex. An important structure on the apical surface of each hair cell is hair bundles divided into two types: actin-based stereociliary bundle and a single tubulin-based kinocilum [2, 3] Another critical part is a specialized actin network known as the cuticular plate, which is located on the apical membrane. Our findings suggest that LKB1 plays an essential role in maintaining normal hearing by regulating the development and maintenance of stereocilia in inner ear hair cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
