Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex.
Amino Acid Sequence
Animals
Base Sequence
Cell Cycle Proteins
/ metabolism
Cytoskeletal Proteins
/ metabolism
Gene Deletion
Hair Cells, Auditory, Inner
/ metabolism
Hearing Loss
/ metabolism
Mechanotransduction, Cellular
Mice, Inbred C57BL
Myosin VIIa
/ chemistry
Protein Isoforms
/ metabolism
Protein Transport
Stereocilia
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
08
04
2019
accepted:
01
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
30
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32350269
doi: 10.1038/s41467-020-15936-z
pii: 10.1038/s41467-020-15936-z
pmc: PMC7190839
doi:
Substances chimiques
Cell Cycle Proteins
0
Cytoskeletal Proteins
0
Myosin VIIa
0
Protein Isoforms
0
Ush1c protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2066Subventions
Organisme : NIDCD NIH HHS
ID : R56 DC017724
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC018457
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC018842
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC017370
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC016868
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM139787
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014254
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 DC000002
Pays : United States
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