Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.
Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.
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塑蛋白1的缺失会导致毛细胞立体胶质的异常维持和小鼠的听力丧失形式。
DOI：
10.1093/hmg/ddu417
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Daudet N
中科院分区：
文献类型：
--
作者：
Taylor R;Bullen A;Johnson SL;Grimm-Günter EM;Rivero F;Marcotti W;Forge A;Daudet N
听觉依赖于Corti器官的机械感觉内毛细胞和外毛细胞（OHC），它们将富含肌动蛋白的静纤毛束的机械偏转转化为电化学信号。一些肌动蛋白相关蛋白是静纤毛形成和维持所必需的，它们的缺失导致耳聋。其中一个最丰富的肌动蛋白捆绑蛋白的静纤毛是plastin 1，但它的功能从来没有被直接评估。在这里，我们发现plastin 1敲除（Pls 1 KO）小鼠在所有频率上都有中度和进行性听力损失。Pls 1基因敲除后听毛细胞发育正常，但在幼年成年动物中，内毛细胞静纤毛的宽度和长度均减少。OHC的静纤毛受到的影响相对较小;然而，它们在衰老小鼠中也显示出退化的迹象。毛束刚度和收购的毛细胞的电生理特性的情况下，不受影响的，除了适应性能的显着变化，但不是机电换能器电流的大小。这些结果表明，与其他肌动蛋白捆绑蛋白，如espin，harmonin或Eps 8相比，plastin 1对于静纤毛的初始形成是不稳定的。然而，进行性听力损失和形态缺陷的毛细胞在成年Pls 1基因敲除小鼠点在一个特定的作用，为plastin 1在保存成年静纤毛和最佳的听力。因此，人类PLS 1基因的突变可能与相对轻度和进行性形式的听力损失有关。
Hearing relies on the mechanosensory inner and outer hair cells (OHCs) of the organ of Corti, which convert mechanical deflections of their actin-rich stereociliary bundles into electrochemical signals. Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness. One of the most abundant actin-bundling proteins of stereocilia is plastin 1, but its function has never been directly assessed. Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and progressive form of hearing loss across all frequencies. Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length. The stereocilia of OHCs were comparatively less affected; however, they also showed signs of degeneration in ageing mice. The hair bundle stiffness and the acquisition of the electrophysiological properties of hair cells were unaffected by the absence of plastin 1, except for a significant change in the adaptation properties, but not the size of the mechanoelectrical transducer currents. These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia. However, the progressive hearing loss and morphological defects of hair cells in adult Pls1 KO mice point at a specific role for plastin 1 in the preservation of adult stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss.
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影响因子：
2.5
作者：
Lelli, Andrea;Asai, Yukako;Geleoc, Gwenaeelle S. G.
通讯作者：
Geleoc, Gwenaeelle S. G.
影响因子：
2.8
作者：
FLOCK, A;BRETSCHER, A;WEBER, K
通讯作者：
WEBER, K
DOI：
10.1098/rspb.1997.0087
发表时间：
1997-04-22
影响因子：
4.7
作者：
Geleoc, GSG;Lennan, GWT;Kros, CJ
通讯作者：
Kros, CJ
DOI：
10.1073/pnas.0900221106
发表时间：
2009-06-16
影响因子：
11.1
作者：
Belyantseva, Inna A.;Perrin, Benjamin J.;Ervasti, James M.
通讯作者：
Ervasti, James M.
影响因子：
--
作者：
Garringer, HJ;Pankratz, ND;Reed, T
通讯作者：
Reed, T