The precise morphology of the mechanosensitive hair bundle requires seamless integration of actin and microtubule networks. Here, we identify Acf7a as a protein positioned to bridge these distinct cytoskeletal networks in hair cells. By imaging Acf7a-Citrine fusion protein in zebrafish and immunolabeling of vestibular and cochlear mouse hair cells, we show that Acf7a and ACF7 circumscribe, underlie, and are interwoven into the cuticular plate (CP), and they also encircle the basal body of the kinocilium. In cochlear hair cells, ACF7 localization is graded, with the highest concentration near each fonticulus-an area free of F-actin in the region of the cuticular plate that contains the basal body. During hair-cell development and regeneration, Acf7a precedes formation of the hair bundle and CP. Finally, electron tomography demonstrates that the ends of microtubules insert into the CP and are decorated with filamentous linkers connecting microtubules to the CP. These observations are consistent with ACF7 being a linker protein, which may shape the hair cell's cytoskeleton early during hair-bundle genesis. This grant proposal further studies the role of this protien in hair bundle formation.
The hair cell is a mechanoreceptor of the inner ear and lateral line system, which is responsible for hearing, balance, and the detection of water movement by some aquatic vertebrates. We have identified a protein that may govern the formation of this intriguing structure called ACF7. In this grant we aim to understand the role of this protein in hearing.
|Chen, Zongwei; Chou, Shih-Wei; McDermott Jr, Brian M (2018) Ribeye protein is intrinsically dynamic but is stabilized in the context of the ribbon synapse. J Physiol 596:409-421|
|Chou, Shih-Wei; Chen, Zongwei; Zhu, Shaoyuan et al. (2017) A molecular basis for water motion detection by the mechanosensory lateral line of zebrafish. Nat Commun 8:2234|
|Vargo, Jonathon W; Walker, Steven N; Gopal, Suhasini R et al. (2017) Inhibition of Mitochondrial Division Attenuates Cisplatin-Induced Toxicity in the Neuromast Hair Cells. Front Cell Neurosci 11:393|
|Pollock, Lana M; Chou, Shih-Wei; McDermott Jr, Brian M (2016) My oh my(osin): Insights into how auditory hair cells count, measure, and shape. J Cell Biol 212:135-7|
|Hwang, Philsang; Chou, Shih-Wei; Chen, Zongwei et al. (2015) The Stereociliary Paracrystal Is a Dynamic Cytoskeletal Scaffold In Vivo. Cell Rep 13:1287-1294|
|Pollock, Lana M; McDermott Jr, Brian M (2015) The cuticular plate: a riddle, wrapped in a mystery, inside a hair cell. Birth Defects Res C Embryo Today 105:126-39|
|Gopal, Suhasini R; Chen, Daniel H-C; Chou, Shih-Wei et al. (2015) Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein. J Neurosci 35:10188-201|
|Antonellis, Patrick J; Pollock, Lana M; Chou, Shih-Wei et al. (2014) ACF7 is a hair-bundle antecedent, positioned to integrate cuticular plate actin and somatic tubulin. J Neurosci 34:305-12|
|Santos-Cortez, Regie Lyn P; Lee, Kwanghyuk; Azeem, Zahid et al. (2013) Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am J Hum Genet 93:132-40|
|Chou, Shih-Wei; Hwang, Philsang; Gomez, Gustavo et al. (2011) Fascin 2b is a component of stereocilia that lengthens actin-based protrusions. PLoS One 6:e14807|