Usher protein functions in hair cells and photoreceptors.
Usher protein functions in hair cells and photoreceptors.
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DOI：
10.1016/j.biocel.2013.11.001
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发表时间：
2014-01
影响因子：
4
通讯作者：
Zallocchi, Marisa
中科院分区：
文献类型：
--
作者：
Cosgrove, Dominic;Zallocchi, Marisa
与失聪/失明障碍相关的10个不同基因，亚瑟综合征，编码了许多结构和功能上不同的蛋白质，大多数以多种异构体/蛋白质变体的形式表达。这些蛋白质的功能特征表明，可能是由于发束中的粘附性相互作用，在耳蜗毛细胞的立体纤毛发育中发挥了作用。在成熟的毛细胞中，Usher钙粘蛋白的同源二聚体--钙粘蛋白23和原钙粘蛋白15相互作用，形成结构纤维、顶端链接和将较高的立体纤毛的肌动蛋白细胞骨架核心固定到较短的相邻立体纤毛和难以捉摸的机械转导通道的链接，解释了当这些分子相互作用受到干扰时耳聋的表型。难题是光感受器缺乏同义的机械转导装置，因此缺乏关于Usher综合征影响的两种神经感觉细胞中Usher蛋白功能的共同理论。最近的证据表明，在Usher综合征的Shaker 1小鼠模型中，光感受器细胞功能障碍与光诱导的蛋白质易位缺陷有关，结合光感受器纤毛区Usher蛋白相互作用组的定位，表明Usher蛋白可能调节光感受器内外节段之间的蛋白质运输。一种独特的Usher蛋白复合体被运输到毛细胞的带状突触，已有报道在毛细胞和光感受器的Usher突变体中发现突触缺陷。该综述旨在阐明Usher蛋白在毛细胞和光感受器的突触和顶端的功能，以及寻找一种统一的病理生物学机制来解释Usher综合征的聋盲的前景。
The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber, the tip link, and the linkages that anchor the taller stereocilia's actin cytoskeleton core to the shorter adjacent stereocilia and the elusive mechanotransduction channels, explaining the deafness phenotype when these molecular interactions are perturbed. The conundrum is that photoreceptors lack a synonymous mechanotransduction apparatus, and so a common theory for Usher protein function in the two neurosensory cell types affected in Usher syndrome is lacking. Recent evidence linking photoreceptor cell dysfunction in the shaker 1 mouse model for Usher syndrome to light-induced protein translocation defects, combined with localization of an Usher protein interactome at the periciliary region of the photoreceptors suggests Usher proteins might regulate protein trafficking between the inner and outer segments of photoreceptors. A distinct Usher protein complex is trafficked to the ribbon synapses of hair cells, and synaptic defects have been reported in Usher mutants in both hair cells and photoreceptors. This review aims to clarify what is known about Usher protein function at the synaptic and apical poles of hair cells and photoreceptors and the prospects for identifying a unifying pathobiological mechanism to explain deaf/blindness in Usher syndrome.
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影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
毛细胞的机械感觉结构需要 clarin-1，这是一种由 Usher 综合征 III 致病基因编码的蛋白质。
DOI：
10.1523/jneurosci.0311-12.2012
发表时间：
2012-07-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Geng R;Melki S;Chen DH;Tian G;Furness DN;Oshima-Takago T;Neef J;Moser T;Askew C;Horwitz G;Holt JR;Imanishi Y;Alagramam KN
通讯作者：
Alagramam KN
DOI：
10.1073/pnas.1130432100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Gibbs, D;Kitamoto, J;Williams, DS
通讯作者：
Williams, DS
影响因子：
4
作者：
El-Amraoui, A;Petit, C
通讯作者：
Petit, C
影响因子：
5.3
作者：
Ahmed ZM;Riazuddin S;Aye S;Ali RA;Venselaar H;Anwar S;Belyantseva PP;Qasim M;Riazuddin S;Friedman TB
通讯作者：
Friedman TB