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Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells


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タイトル: Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells
著者: Ueyama, Takehiko / Sakaguchi, Hirofumi / Nakamura, Takashi / Goto, Akihiro / Morioka, Shigefumi / Shimizu, Aya / Nakao, Kazuki / Hishikawa, Yoshitaka / Ninoyu, Yuzuru / Kassai, Hidetoshi / Suetsugu, Shiro / Koji, Takehiko / Fritzsch, Bernd / Yonemura, Shigenobu / Hisa, Yasuo / Matsuda, Michiyuki / Aiba, Atsu / Saito, Naoaki
発行日: 2014年 5月
出版者: Company of Biologists Ltd
引用: Journal of Cell Science, 127(9), pp.2040-2052; 2014
抄録: Cdc42 is a key regulator of dynamic actin organization. However, little is known about how Cdc42-dependent actin regulation influences steady-state actin structures in differentiated epithelia. We employed inner ear hair-cell-specific conditional knockout to analyze the role of Cdc42 in hair cells possessing highly elaborate stable actin protrusions (stereocilia). Hair cells of Atoh1-Cre;Cdc42flox/flox mice developed normally but progressively degenerated after maturation, resulting in progressive hearing loss particularly at high frequencies. Cochlear hair cell degeneration was more robust in inner hair cells than in outer hair cells, and began as stereocilia fusion and depletion, accompanied by a thinning and waving circumferential actin belt at apical junctional complexes (AJCs). Adenovirus-encoded GFP-Cdc42 expression in hair cells and fluorescence resonance energy transfer (FRET) imaging of hair cells from transgenicmice expressing a Cdc42-FRET biosensor indicated Cdc42 presence and activation at stereociliary membranes and AJCs in cochlear hair cells. Cdc42-knockdown in MDCK cells produced phenotypes similar to those of Cdc42-deleted hair cells, including abnormal microvilli and disrupted AJCs, and downregulated actin turnover represented by enhanced levels of phosphorylated cofilin. Thus, Cdc42 influenced the maintenance of stable actin structures through elaborate tuning of actin turnover, and maintained function and viability of cochlear hair cells.
キーワード: Actin turnover / Apical junctional complex / Cdc42 / Deafness / Fret / Hair cell / Stereocilia
URI: http://hdl.handle.net/10069/34499
ISSN: 00219533
DOI: 10.1242/jcs.143602
権利: © 2014. Published by The Company of Biologists Ltd / This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:030 学術雑誌論文

引用URI : http://hdl.handle.net/10069/34499

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