@article{6e1d15463eb3459da652620350d426e7,
title = "XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia",
abstract = "Hair cells of the inner ear are mechanoreceptors for hearing and balance, and proteins highly enriched in hair cells may have specific roles in the development and maintenance of the mechanotransduction apparatus. We identified XIRP2/mXinβ as an enriched protein likely to be essential for hair cells. We found that different isoforms of this protein are expressed and differentially located: short splice forms (also called XEPLIN) are targeted more to stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal stereocilia bundles, but these degenerated with time: stereocilia were lost and long membranousprotrusions emanated from the nearby apical surfaces. At an ultrastructural level, the paracrystalline actin filaments became disorganized. XIRP2 isapparently involved in the maintenance of actin structures in stereocilia and cuticular plates of haircells, and perhaps in other organs where it is expressed.",
author = "Scheffer, {D{\'e}borah I.} and Zhang, {Duan Sun} and Jun Shen and Artur Indzhykulian and Karavitaki, {K. Domenica} and Xu, {Yichao Joy} and Qinchuan Wang and Lin, {Jim Jung Ching} and Chen, {Zheng Yi} and Corey, {David P.}",
note = "Funding Information: We appreciate help with FM1-43 loading from Paul Niksch at Harvard Medical School, help with initial auditory brainstem response tests on another XIRP2 mutant from Sharon Kujawa at Massachusetts Eye and Ear, advice on image analysis from Hunter Elliott and Tiao Xie at the Harvard Medical School Image and Data Analysis Core, and electron microscopy support from Louise Trakimas at Harvard Medical School and William Fowle at Northeastern University. We appreciate a PMCA2 antibody from Peter Barr-Gillespie at Oregon Health & Science University and a XIRP2 antibody from Francisco Naya at Boston University. We thank Andy Sharpe and Chris Bennet at the University of Leeds (UK) for providing us with the DFNB27 family DNAs. We thank the Harvard Neurobiology Imaging Facility (a part of the Neural Imaging Center supported by NINDS P30 Core Center grant NS072030) for consultation and instrumentation. This research was supported by NIH grants R01-DC000304 and R01-DC002281 (to D.P.C.), R01-DC006908 (to Z.-Y.C.), P30-DC05209 to the Massachusetts Eye and Ear, RO1-HL107383 (to J.J.-C.L.), and a Frederick and Ines Yeatts Hair Cell Regeneration grant (to Z.-Y.C.). D.P.C. is an investigator and K.D.K. and D.-S.Z. were associates of the Howard Hughes Medical Institute. We thank Dr. Lisa Goodrich for helpful comments on the manuscript. Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = mar,
day = "24",
doi = "10.1016/j.celrep.2015.02.042",
language = "English (US)",
volume = "10",
pages = "1811--1818",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}