Cochlear supporting cells require GAS2 for cytoskeletal architecture and hearing
| Autor: | Hannie Kremer, Kevin K. Ohlemiller, Staci M. Rakowiecki, Christian Gilissen, Jiddeke M. van de Kamp, Erdi Kucuk, Alex M Rohacek, Jeroen Smits, Jaap Oostrik, Amir Nankali, John S. Oghalai, Benjamin L. Prosser, Douglas J. Epstein, Klaus H. Kaestner, Tingfang Chen, Cornelis P. Lanting, Matthew A. Caporizzo, Ronald J.E. Pennings |
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| Přispěvatelé: | Clinical genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2021 |
| Předmět: |
Hearing loss
Cochlear duct Biology Microtubules Vibration Article General Biochemistry Genetics and Molecular Biology Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] 03 medical and health sciences 0302 clinical medicine All institutes and research themes of the Radboud University Medical Center Hearing Microtubule Hair Cells Auditory Exome Sequencing medicine otorhinolaryngologic diseases Animals Humans Inner ear Amino Acid Sequence Hearing Loss Cytoskeleton Molecular Biology Cochlea 030304 developmental biology Regulation of gene expression 0303 health sciences Base Sequence Microfilament Proteins Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Cell Biology Cell biology Mice Inbred C57BL Protein Transport Sound medicine.anatomical_structure Animals Newborn Mutation sense organs medicine.symptom Microtubule bundle 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell, 56, 10, pp. 1526-1540.e7 Dev Cell Developmental Cell, 56, 1526-1540.e7 Chen, T, Rohacek, A M, Caporizzo, M, Nankali, A, Smits, J J, Oostrik, J, Lanting, C P, Kücük, E, Gilissen, C, van de Kamp, J M, Pennings, R J E, Rakowiecki, S M, Kaestner, K H, Ohlemiller, K K, Oghalai, J S, Kremer, H, Prosser, B L & Epstein, D J 2021, ' Cochlear supporting cells require GAS2 for cytoskeletal architecture and hearing ', Developmental Cell, vol. 56, no. 10, pp. 1526-1540.e7 . https://doi.org/10.1016/j.devcel.2021.04.017 Developmental Cell, 56(10), 1526-1540.e7. Cell Press |
| ISSN: | 1534-5807 1878-1551 |
| DOI: | 10.1016/j.devcel.2021.04.017 |
| Popis: | In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea. |
| Databáze: | OpenAIRE |
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