Super-resolution microscopy reveals altered desmosomal protein organization in pemphigus vulgaris patient tissue
Super-resolution microscopy reveals altered desmosomal protein organization in pemphigus vulgaris patient tissue
复制标题
超分辨率显微镜揭示寻常型天疱疮患者组织中桥粒蛋白组织的改变
DOI：
--
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发表时间：
2015
影响因子：
6.5
通讯作者：
A. Kowalczyk
中科院分区：
文献类型：
--
作者：
S. Stahley;M. Warren;R. Feldman;R. Swerlick;A. Mattheyses;A. Kowalczyk
寻常天疱疮（PV）是一种自身免疫性表皮起泡疾病，其中自身抗体（IgG）针对桥粒钙粘蛋白桥粒芯蛋白3（Dsg 3）。为了更好地了解PV IgG如何改变体内桥粒形态和功能，通过结构化照明显微镜（SIM）（一种超分辨率荧光显微镜）分析PV患者活检组织。在患者组织中，桥粒蛋白异常聚集并定位于含有PV IgG的内吞线性阵列。患者IgG还与脂筏和内体的标志物共定位。此外，患者组织中Dsg3的稳态水平降低，桥粒尺寸减小。水泡部位的桥粒偶尔分裂，PV IgG装饰分裂的桥粒的细胞外表面。通过将培养的角质形成细胞暴露于PV IgG和机械应力，在体外重现了桥粒分裂，表明患者组织中水疱界面处的分裂是由于桥粒粘附功能受损。这些发现表明Dsg3聚集和内吞作用与PV患者组织中桥粒尺寸减小和粘附缺陷相关。此外，这项研究表明，超分辨率光学成像是研究正常和病变皮肤表皮粘附结构的有力手段。
Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3 (Dsg3). In order to better understand how PV IgG alters desmosome morphology and function in vivo, PV patient biopsies were analyzed by structured illumination microscopy (SIM), a form of super-resolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and localized to PV IgG-containing endocytic linear arrays. Patient IgG also colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of Dsg3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue. Further, this study reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin.
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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：
--
DOI：
10.1016/b978-0-12-394311-8.00005-4
发表时间：
2013
影响因子：
--
作者：
Kowalczyk, Andrew P.;Green, Kathleen J.
通讯作者：
Green, Kathleen J.
影响因子：
7.2
作者：
Shapiro, Lawrence;Weis, William I.
通讯作者：
Weis, William I.
桥粒斑块的分子图。
影响因子：
4
作者：
North,AJ;Bardsley,WG;Hyam,J;Bornslaeger,EA;Cordingley,HC;Trinnaman,B;Hatzfeld,M;Green,KJ;Magee,AI;Garrod,DR
通讯作者：
Garrod,DR
影响因子：
19
作者：
Nekrasova, Oxana;Green, Kathleen J.
通讯作者：
Green, Kathleen J.