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.
Tatsuya Katsuno, Inna A. Belyantseva, Alexander X. Cartagena-Rivera, Keisuke Ohta, Shawn M. Crump, Ronald S. Petralia, Kazuya Ono, Risa Tona, Ayesha Imtiaz, Atteeq Rehman, Hiroshi Kiyonari, Mari Kaneko, Ya-Xian Wang, Takaya Abe, Makoto Ikeya, Cristina Fenollar-Ferrer, Gavin P. Riordan, Elisabeth A. Wilson, Tracy S. Fitzgerald, Kohei Segawa, Koichi Omori, Juichi Ito, Gregory I. Frolenkov, Thomas B. Friedman, Shin-ichiro Kitajiri
Usage data is cumulative from September 2021 through September 2022.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.