Actin cytoskelton regulation in the inner ear
Description: Mice lacking both TRIOBP-4 and TRIOBP-5 are profoundly congenitally deaf by loss of rootlets. In transgenic Triobp-4GFP mice, GFP-TRIOBP-4 localizes to rootlet segments within stereocilia. TRIOBP-5 homo-multimerizes and concentrates in rootlet segments embedded in the cuticular plate. Strikingly, TRIOBP-5 specific deficient mutants (TRIOBP-5 KO) show progressive hearing loss and develop dysmorphic, fragile stereocilia rootlets. During fluid-jet stimulation of increasing intensity, Triobp-5 KO stereocilia bundles of hair cells show increased pivotal-flexibility and susceptibility to damage. Atomic Force Microscopy detected a two-fold decreased apical surface stiffness in live TRIOBP-5 KO supporting cells. Thus, stereocilia rootlet formation requires TRIOBP-4, while TRIOBP-5 reinforces rootlets for life-long acoustical stimulation and also provides force-homeostasis across the sensory epithelium.
Amount: ¥15,730,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (B)
Start date: 2014-04-01
End date: 2018-03-31
Investigator: Shin-ichiro Kitajiri
Institution: Shinshu University(2017)Kyoto University(2014-2016)
Funded outputs count: 6
Funder award ID: 26293369
OpenAlex ID: G8404668302