A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles

被引:2
作者
Tompkins, Nathan [1 ,2 ,5 ]
Spinelli, Kateri J. [1 ,2 ,6 ]
Choi, Dongseok [3 ,4 ]
Barr-Gillespie, Peter G. [1 ,2 ]
机构
[1] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA
[2] Oregon Hlth & Sci Univ, Vollum Inst, L474, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97201 USA
[4] Kyung Hee Univ, Grad Sch Dent, Seoul, South Korea
[5] Wabash Coll, Dept Phys, Crawfordsville, IN USA
[6] Providence Portland Med Ctr, Portland, OR USA
基金
美国国家卫生研究院;
关键词
CELL STEREOCILIA; MECHANOELECTRICAL TRANSDUCTION; MECHANICAL TRANSDUCTION; FUNCTIONAL INTERACTION; SENSORY TRANSDUCTION; FAST ADAPTATION; N-CADHERIN; CHANNELS; MECHANOTRANSDUCTION; MYOSIN-1C;
D O I
10.1016/j.bpj.2017.08.029
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Tip links are thought to gate the mechanically sensitive transduction channels of hair cells, but how they form during development and regeneration remains mysterious. In particular, it is unclear how tip links are strung between stereocilia so that they are oriented parallel to a single axis; why their polarity is uniform despite their constituent molecules' intrinsic asymmetry; and why only a single tip link is present at each tip-link position. We present here a series of simple rules that reasonably explain why these phenomena occur. In particular, our model relies on each of the two ends of the tip link having distinct Ca2+-dependent stability and being connected to different motor complexes. A simulation employing these rules allowed us to explore the parameter space for the model, demonstrating the importance of the feedback between transduction channels and angled links, links that are 60 degrees off-axis with respect to mature tip links. We tested this key aspect of the model by examining angled links in chick cochlea hair cells. As implied by the assumptions used to generate the model, we found that angled links were stabilized if there was no tip link at the tip of the upper stereocilium, and appeared when transduction channels were blocked. The model thus plausibly explains how tip-link formation and pruning can occur.
引用
收藏
页码:1868 / 1881
页数:14
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