The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.
The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.
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原粘蛋白15的CD2同工型是成熟听觉毛细胞中尖端连接复合物的重要组成部分。
DOI：
10.15252/emmm.201403976
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发表时间：
2014-07
影响因子：
11.1
通讯作者：
Petit C
中科院分区：
文献类型：
--
作者：
Pepermans E;Michel V;Goodyear R;Bonnet C;Abdi S;Dupont T;Gherbi S;Holder M;Makrelouf M;Hardelin JP;Marlin S;Zenati A;Richardson G;Avan P;Bahloul A;Petit C
原钙粘蛋白-15（Pcdh 15）是tip-links的一个组成部分，tip-links是内耳毛细胞机械-电转导通道的细胞外细丝。Pcdh 15剪接有三种亚型（CD 1、CD 2和CD 3），它们的区别仅在于胞质结构域;它们被认为在毛束发育过程中在机械电转导中发挥冗余作用，但这些亚型中是否有任何一种构成成熟毛细胞中的尖端连接仍然未知。通过对出生后毛细胞特异性条件性敲除小鼠（Pcdh 15 ex 38-fl/ex 38-fl Myo 15-cre+/−）的免疫标记以及形态学和电生理学分析，我们发现Pcdh 15-CD 2是成熟听毛细胞中tip-links的重要组成部分。在来自两个不相关家族的重度耳聋儿童中，在纯合或复合杂合状态下发现了仅影响Pcdh 15-CD 2的PCDH 15移码突变（p.P1515Tfs*4），将这一结论扩展到人类。这些结果为识别成熟的听觉机械-电转换机制的新成分提供了关键信息。这也将为PCDH 15缺陷引起的耳聋的基因治疗的发展奠定基础。
Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular filaments that gate hair cell mechano-electrical transduction channels in the inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cytoplasmic domains; they are thought to function redundantly in mechano-electrical transduction during hair-bundle development, but whether any of these isoforms composes the tip-link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15-cre+/−) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15 frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano-electrical transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects.
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影响因子：
2.5
作者：
Goodyear, Richard J.;Forge, Andy;Legan, P. Kevin;Richardson, Guy P.
通讯作者：
Richardson, Guy P.
影响因子：
4.6
作者：
Webb, Stuart W.;Grillet, Nicolas;Mueller, Ulrich
通讯作者：
Mueller, Ulrich
影响因子：
3.5
作者：
Delmaghani, Sedigheh;Aghaie, Asadollah;Petit, Christine
通讯作者：
Petit, Christine
影响因子：
3.7
作者：
Bonnet C;Grati M;Marlin S;Levilliers J;Hardelin JP;Parodi M;Niasme-Grare M;Zelenika D;Délépine M;Feldmann D;Jonard L;El-Amraoui A;Weil D;Delobel B;Vincent C;Dollfus H;Eliot MM;David A;Calais C;Vigneron J;Montaut-Verient B;Bonneau D;Dubin J;Thauvin C;Duvillard A;Francannet C;Mom T;Lacombe D;Duriez F;Drouin-Garraud V;Thuillier-Obstoy MF;Sigaudy S;Frances AM;Collignon P;Challe G;Couderc R;Lathrop M;Sahel JA;Weissenbach J;Petit C;Denoyelle F
通讯作者：
Denoyelle F
影响因子：
3
作者：
Lallemand, Y;Luria, V;Lonai, P
通讯作者：
Lonai, P