Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex
| Autor: | Andrew A. Mecca, Jeewoo Kim, Giusy A. Caprara, Bechara Kachar, Ivan T. Rebustini, Sihan Li, Elizabeth L. Wagner, Anthony W. Peng, Runjia Cui, Wenhao Xu, Ting-Ting Du, Jung-Bum Shin, Leonid Petrov |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Cell biology MYO7A Molecular biology Science General Physics and Astronomy Cell Cycle Proteins macromolecular substances Biology Mechanotransduction Cellular General Biochemistry Genetics and Molecular Biology Article Stereocilia 03 medical and health sciences 0302 clinical medicine medicine otorhinolaryngologic diseases Animals Protein Isoforms Amino Acid Sequence Mechanotransduction lcsh:Science Hearing Loss Peptide sequence Cochlea Multidisciplinary Hair Cells Auditory Inner Base Sequence General Chemistry Transport protein Mice Inbred C57BL Cytoskeletal Proteins Protein Transport 030104 developmental biology medicine.anatomical_structure Myosin VIIa lcsh:Q Hair cell sense organs Tip link 030217 neurology & neurosurgery Gene Deletion Neuroscience |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Mutations in myosin-VIIa (MYO7A) cause Usher syndrome type 1, characterized by combined deafness and blindness. MYO7A is proposed to function as a motor that tensions the hair cell mechanotransduction (MET) complex, but conclusive evidence is lacking. Here we report that multiple MYO7A isoforms are expressed in the mouse cochlea. In mice with a specific deletion of the canonical isoform (Myo7a-ΔC mouse), MYO7A is severely diminished in inner hair cells (IHCs), while expression in outer hair cells is affected tonotopically. IHCs of Myo7a-ΔC mice undergo normal development, but exhibit reduced resting open probability and slowed onset of MET currents, consistent with MYO7A’s proposed role in tensioning the tip link. Mature IHCs of Myo7a-ΔC mice degenerate over time, giving rise to progressive hearing loss. Taken together, our study reveals an unexpected isoform diversity of MYO7A expression in the cochlea and highlights MYO7A’s essential role in tensioning the hair cell MET complex. How the ear achieves its remarkable sensitivity is still not fully understood. In this study, the authors demonstrate that the deafness protein myosin-VIIa and its isoforms are essential for tensioning the tip link, thereby sensitizing the auditory receptor cell’s mechanotransduction process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|