Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, 25 Rue du Dr Roux, 75015 Paris, France.
Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a003095. doi: 10.1101/cshperspect.a003095.
The 6-billion human population provides a vast reservoir of mutations, which, in addition to the opportunity of detecting very subtle defects, including specific cognitive dysfunctions as well as late appearing disorders, offers a unique background in which to investigate the roles of cell-cell adhesion proteins. Here we focus on inherited human disorders involving members of the cadherin superfamily. Most of the advances concern monogenic disorders. Yet, with the development of single nucleotide polymorphism (SNP) association studies, cadherin genes are emerging as susceptibility genes in multifactorial disorders. Various skin and heart disorders revealed the critical role played by desmosomal cadherins in epidermis, hairs, and myocardium, which experience high mechanical stress. Of particular interest in that respect is the study of Usher syndrome type 1 (USH1), a hereditary syndromic form of deafness. Studies of USH1 brought to light the crucial role of transient fibrous links formed by cadherin 23 and protocadherin 15 in the cohesion of the developing hair bundle, the mechanoreceptive structure of the auditory sensory cells, as well as the involvement of these cadherins in the formation of the tip-link, a key component of the mechano-electrical transduction machinery. Finally, in line with the well-established role of cadherins in synaptic formation, maintenance, strength, and plasticity, a growing number of cadherin family members, especially protocadherins, have been found to be involved in neuropsychiatric disorders.
60 亿人口为基因突变提供了巨大的储备，这不仅提供了检测非常细微缺陷的机会，包括特定的认知功能障碍和后期出现的疾病，还为研究细胞间黏附蛋白的作用提供了独特的背景。在这里，我们重点关注涉及钙黏蛋白超家族成员的遗传性人类疾病。大多数进展都涉及单基因疾病。然而，随着单核苷酸多态性 (SNP) 关联研究的发展，钙黏蛋白基因作为多因素疾病的易感基因正在出现。各种皮肤和心脏疾病揭示了桥粒钙黏蛋白在经历高机械应力的表皮、毛发和心肌中所起的关键作用。在这方面特别有趣的是对 1 型Usher 综合征 (USH1) 的研究，这是一种遗传性耳聋综合征。对 USH1 的研究揭示了钙黏蛋白 23 和原钙黏蛋白 15 形成的短暂纤维连接在发育中的毛束粘着、听觉感觉细胞的机械感受器结构中的关键作用，以及这些钙黏蛋白在形成尖端连接中的作用，尖端连接是机械-电转导机制的关键组成部分。最后，与钙黏蛋白在突触形成、维持、强度和可塑性中的既定作用一致，越来越多的钙黏蛋白家族成员，特别是原钙黏蛋白，被发现与神经精神疾病有关。
