期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：13958-13963
DOI：10.1073/pnas.2334417100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mutations of the gene encoding unconventional myosin XVa are associated with sensorineural deafness in humans (DFNB3) and shaker (Myo15sh2) mice. In deaf Myo15sh2/sh2 mice, stereocilia are short, nearly equal in length, and lack myosin XVa immunoreactivity. We previously reported that myosin XVa mRNA and protein are expressed in cochlear hair cells. We now show that in the mouse, rat, and guinea pig, endogenous myosin XVa localizes to the tips of the stereocilia of the cochlear and vestibular hair cells. Myosin XVa localization overlaps with the barbed ends of actin filaments and extends to the apical plasma membrane of the stereocilia. Gene gun-mediated transfection of mouse inner ear sensory epithelia explants shows selective accumulation of myosin XVa-GFP at the tips of stereocilia, confirming the localization of native myosin XVa. Expression in COS7 cells also reveals targeting of myosin XVa-GFP to the dynamic actin region at the tips of filopodia. In a wild-type mouse, during auditory and vestibular hair cell development, myosin XVa appears at the tips of stereocilia at the time when the hair bundle begins to develop its characteristic staircase pattern. We propose that myosin XVa is essential for the graded elongation of stereocilia during their functional maturation.
