TUBB4B is essential for the cytoskeletal architecture of cochlear supporting cells and motile cilia development.

Autor: Sanzhaeva U; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA., Boyd-Pratt H; Clinical Translational Sciences Institute, West Virginia University School of Medicine, Morgantown, WV, USA., Bender PTR; Rockefeller Neuroscience Institute and Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA., Saravanan T; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA., Rhodes SB; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA., Guan T; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA., Billington N; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA., Boye SE; Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA., Cunningham CL; Pittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., Anderson CT; Rockefeller Neuroscience Institute and Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA., Ramamurthy V; Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, USA. ramamurthyv@hsc.wvu.edu.; Department of Ophthalmology and Visual Sciences, West Virginia University School of Medicine, Morgantown, WV, USA. ramamurthyv@hsc.wvu.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Sep 14; Vol. 7 (1), pp. 1146. Date of Electronic Publication: 2024 Sep 14.
DOI: 10.1038/s42003-024-06867-2
Abstrakt: Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and β-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of β4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b -/- mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, β6-tubulin levels increase in retinas lacking β4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.
(© 2024. The Author(s).)
Databáze: MEDLINE
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