Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function

• Main Authors: Bo Zhao, Zizhen Wu, Ulrich Müller
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-06-01
• Series: eLife
• Subjects: hearing; deafness; mechanotransduction; sterocilia; STORM; Fam65b
• Online Access: https://elifesciences.org/articles/14222

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.