Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function.
Cochlear hair cells convert sound-induced vibration into electrical signals. FAM65B mutations cause hearing loss by an unknown mechanism. Using biochemistry and stochastic optical reconstruction microscopy (STORM), we show here that Fam65b oligomers form a circumferential ring near the basal taper of the mechanically sensitive stereocilia of murine hair cells. Taperin, a second protein near the taper, forms a dense-core-like structure that is disrupted in the absence of Fam65b. Stereocilia of Fam65b-deficient murine hair cells start to develop, but mechanotransduction is affected and stereocilia deteriorate. Yeast-two-hybrid screens identify RhoC as a Fam65b binding partner. RhoC co-localizes with Fam65b in stereocilia and regulates Fam65b oligomerization. Binding to RhoC and oligomerization are critical for Fam65b function. Our findings thus reveal a highly organized compartment near the base of stereocilia that is critical for hair cell function and affected in disease.
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, United States.|Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States.
Bo
B
Zhao
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, United States.|Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States.
Zizhen
Z
Wu
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, United States.|Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States.
Ulrich
0000-0003-2736-6494
U
Müller
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D055786:Gene Knockout Techniques; D054777:Hair Cells, Ampulla / Q000502:physiology*; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008853:Microscopy; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D011506:Proteins / Q000378:metabolism; D059547:Stereocilia / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000075024:rhoC GTP-Binding Protein / Q000378:metabolism*
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C000624891:FAM65B protein, mouse; D008565:Membrane Proteins; D011506:Proteins; C548552:taperin protein, mouse; C512911:Rhoc protein, mouse; D000075024:rhoC GTP-Binding Protein
Fam65b; STORM; deafness; hearing; mechanotransduction; mouse; neuroscience; sterocilia