Desmosome assembly and disassembly are membrane raft-dependent.
Desmosome assembly and disassembly are membrane raft-dependent.
复制标题
桥粒组装和拆卸依赖于膜筏。
DOI：
10.1371/journal.pone.0087809
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kowalczyk AP
中科院分区：
文献类型：
--
作者：
Stahley SN;Saito M;Faundez V;Koval M;Mattheyses AL;Kowalczyk AP
强烈的细胞间粘附对于经受机械压力的组织，如皮肤和心脏，是至关重要的。桥粒通过将相邻细胞的桥粒钙粘蛋白锚定在中间丝细胞骨架上，为组织提供粘附力。组装和拆卸的改变会损害桥粒的功能，并可能导致人类疾病，如自身免疫性皮肤起疱性疾病寻常性天疱疮（PV）。我们之前已经证明，针对桥粒钙粘蛋白桥粒蛋白3 （Dsg3）的PV自身抗体通过触发膜筏介导的Dsg3内吞作用导致粘附丧失。我们假设筏膜微结构域通过调节桥粒组装和拆卸的动力学，在桥粒稳态中发挥更广泛的作用。在人角质形成细胞中，通过生化和超分辨率免疫荧光显微镜方法确定Dsg3是紧密相关的。胆固醇消耗，破坏筏，阻止桥粒组装和粘附，从而功能连接筏桥粒形成。有趣的是，Dsg3在缺乏桥粒体蛋白的细胞中不与筏相关。此外，PV igg诱导的桥粒解体发生在Dsg3重新分布到含有筏的内吞膜区域，导致胆固醇依赖性的粘附丧失。这些发现表明，膜筏是桥粒组装和拆卸动力学所必需的，这表明膜筏靶向药物在桥粒疾病（如PV）中的治疗潜力。
Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart. Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton. Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV). We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis. We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly. In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods. Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation. Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins. Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion. These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV.
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DOI：
10.1038/jid.2010.389
发表时间：
2011-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Delva, Emmanuella;Jennings, Jean Marie;Kowalczyk, Andrew P.
通讯作者：
Kowalczyk, Andrew P.
DOI：
10.2183/pjab.86.524
发表时间：
2010
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Amagai M
通讯作者：
Amagai M
影响因子：
7.8
作者：
DROCHMANS, P;FREUDENSTEIN, C;FRANKE, WW
通讯作者：
FRANKE, WW
影响因子：
3.3
作者：
Causeret, M;Taulet, N;Gauthier-Rouvière, C
通讯作者：
Gauthier-Rouvière, C