A chemical-genetic strategy implicates myosin-1c in adaptation by hair cells

被引:252
作者
Holt, JR
Gillespie, SKH
Provance, DW
Shah, K
Shokat, KM
Corey, DP
Mercer, JA
Gillespie, PG [1 ]
机构
[1] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA
[3] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA
[4] McLaughlin Res Inst, Great Falls, MT 59405 USA
[5] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA
[6] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[7] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA
关键词
D O I
10.1016/S0092-8674(02)00629-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myosin-1c (also known as myosin-1beta) has been proposed to mediate the slow component of adaptation by hair cells, the sensory cells of the inner ear. To test this hypothesis, we mutated tyrosine-61 of myosin-1c to glycine, conferring susceptibility to inhibition by N-6-modified ADP analogs. We expressed the mutant myosin-1c in utricular hair cells of transgenic, mice, delivered an ADP analog through a whole-cell recording pipette, and found that the analog rapidly blocked adaptation to positive and negative deflections in transgenic cells but not in wild-type cells. The speed and specificity of inhibition suggests that myosin-1c participates in adaptation in hair cells.
引用
收藏
页码:371 / 381
页数:11
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