Stratifin (14-3-3 σ) limits plakophilin-3 exchange with the desmosomal plaque.
Stratifin (14-3-3 σ) limits plakophilin-3 exchange with the desmosomal plaque.
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DOI：
10.1371/journal.pone.0077012
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wahl JK 3rd
中科院分区：
文献类型：
--
作者：
Roberts BJ;Reddy R;Wahl JK 3rd
桥粒是复层鳞状上皮中突出的细胞-细胞粘附连接，并且已经显示桥粒粘附的破坏对这些组织的功能和完整性具有显著影响。在正常的生理过程中，如组织发育和伤口愈合，细胞间的粘附必须局部改变，以允许协调的细胞运动。在这些条件下控制连接完整性和粘合强度的机制知之甚少。我们利用蛋白质组学的方法来确定plakophilin-3相关的蛋白质，并确定了14-3-3家庭成员分层。Stratifin与斑嗜蛋白-3特异性相互作用，而不与其他斑嗜蛋白同种型相互作用，突变分析表明结合位点包括斑嗜蛋白-3的氨基末端头部结构域中的丝氨酸285。分层与plakophilin-3的细胞质池相互作用，并且与培养细胞中的桥粒无关。FRAP分析显示，分层蛋白表达减少导致细胞质中的斑嗜蛋白-3/GFP与桥粒中的斑嗜蛋白-3/GFP池的交换率增加，从而导致桥粒粘附减少和细胞迁移增加。我们提出了一个模型，分层起着调节plakophilin-3纳入到桥粒斑块的作用，形成一个plakophilin-3分层复合物在胞质溶胶中，从而影响鳞状上皮细胞中的桥粒动力学。
Desmosomes are prominent cell-cell adhesive junctions in stratified squamous epithelia and disruption of desmosomal adhesion has been shown to have dramatic effects on the function and integrity of these tissues. During normal physiologic processes, such as tissue development and wound healing, intercellular adhesion must be modified locally to allow coordinated cell movements. The mechanisms that control junction integrity and adhesive strength under these conditions are poorly understood. We utilized a proteomics approach to identify plakophilin-3 associated proteins and identified the 14-3-3 family member stratifin. Stratifin interacts specifically with plakophilin-3 and not with other plakophilin isoforms and mutation analysis demonstrated the binding site includes serine 285 in the amino terminal head domain of plakophilin-3. Stratifin interacts with a cytoplasmic pool of plakophilin-3 and is not associated with the desmosome in cultured cells. FRAP analysis revealed that decreased stratifin expression leads to an increase in the exchange rate of cytoplasmic plakophilin-3/GFP with the pool of plakophilin-3/GFP in the desmosome resulting in decreased desmosomal adhesion and increased cell migration. We propose a model by which stratifin plays a role in regulating plakophilin-3 incorporation into the desmosomal plaque by forming a plakophilin-3 stratifin complex in the cytosol and thereby affecting desmosome dynamics in squamous epithelial cells.
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