Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid.

Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid.
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DOI:
10.1083/jcb.201606036
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发表时间:
2016-11-21
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Barr-Gillespie PG
Barr-Gillespie PG
中科院分区:
其他
文献类型:
--
作者:
Krey JF;Krystofiak ES;Dumont RA;Vijayakumar S;Choi D;Rivero F;Kachar B;Jones SM;Barr-Gillespie PG

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内耳感觉毛细胞的立体纤毛充满了平行肌动蛋白细丝的准晶体阵列。Krey等人。结果表明,肌动蛋白交联剂pltin-1是肌动蛋白细丝和最终立体纤毛直径随机液体堆积所必需的。感觉毛细胞的纤毛在内耳功能中起着至关重要的作用,说明了细胞肌动蛋白突起的重要性。肌动蛋白在立体纤毛中的堆积是由纤溶酶、法菌素和ESpin家族的交联物介导的。虽然缺乏ESpin(ESPN)的小鼠没有前庭或听觉功能,但我们发现缺乏纤溶酶1(PLS1)或具有无功能的Fasin 2(FSCN2)的小鼠内耳功能下降,其中双突变小鼠受到的影响最大。靶向质谱学分析表明,∼是前庭纤毛中含量最丰富的交联物,也是第二丰富的蛋白质,ESPN仅占交联物总量的15%。缺失PLS1的小鼠胞果体纤毛比野生型体纤毛更短、更薄。令人惊讶的是,尽管野生型立体纤毛的肌动蛋白细丝有随机的液体堆积,但缺乏PLS1的立体纤毛具有有序的六角形堆积。虽然所有三种交联剂都是立体纤毛结构和功能所必需的,但PLS1使肌动蛋白偏向液体填料,从而使立体纤毛生长到更大的直径。
Stereocilia of the inner ear’s sensory hair cells are filled with a paracrystalline array of parallel actin filaments. Krey et al. show that the actin cross-linker plastin-1 is needed for random liquid packing of actin filaments and final stereocilia diameter. With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.
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