TRIOBP-5 sculpts stereocilia rootlets and stiffens supporting cells enabling hearing.
Cytoskeleton
Neuroscience
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
20 06 2019
20 06 2019
Historique:
received:
04
03
2019
accepted:
08
05
2019
entrez:
21
6
2019
pubmed:
21
6
2019
medline:
25
8
2020
Statut:
epublish
Résumé
TRIOBP remodels the cytoskeleton by forming unusually dense F-actin bundles and is implicated in human cancer, schizophrenia, and deafness. Mutations ablating human and mouse TRIOBP-4 and TRIOBP-5 isoforms are associated with profound deafness, as inner ear mechanosensory hair cells degenerate after stereocilia rootlets fail to develop. However, the mechanisms regulating formation of stereocilia rootlets by each TRIOBP isoform remain unknown. Using 3 new Triobp mouse models, we report that TRIOBP-5 is essential for thickening bundles of F-actin in rootlets, establishing their mature dimensions and for stiffening supporting cells of the auditory sensory epithelium. The coiled-coil domains of this isoform are required for reinforcement and maintenance of stereocilia rootlets. A loss of TRIOBP-5 in mouse results in dysmorphic rootlets that are abnormally thin in the cuticular plate but have increased widths and lengths within stereocilia cores, and causes progressive deafness recapitulating the human phenotype. Our study extends the current understanding of TRIOBP isoform-specific functions necessary for life-long hearing, with implications for insight into other TRIOBPopathies.
Identifiants
pubmed: 31217345
pii: 128561
doi: 10.1172/jci.insight.128561
pmc: PMC6629139
doi:
pii:
Substances chimiques
Actins
0
Microfilament Proteins
0
Protein Isoforms
0
TRIOBP protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Intramural NIH HHS
ID : ZIC DC000081
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014658
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA MH002946
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC000039
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 DC000039
Pays : United States
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