PLAC1 affects cell to cell communication by interacting with the desmosome complex.
PLAC1 affects cell to cell communication by interacting with the desmosome complex.
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DOI：
10.1016/j.placenta.2021.06.001
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发表时间：
2021-07
期刊：
影响因子：
3.8
通讯作者：
Nagaraja R
中科院分区：
文献类型：
--
作者：
Chen Y;Stagg C;Schlessinger D;Nagaraja R
X连锁PLAC1在胚胎发生过程中在胎盘中高度表达，当在小鼠体内被消除时，会导致胎盘细胞层组织异常。它在多种类型的癌细胞系中也高度表达。尽管已证明它能促进癌细胞中的 AKT 磷酸化，但其影响胎盘层分化的确切机制尚不清楚。为了研究 PLAC1 的作用机制，我们对蛋白质进行了细胞分级分离和免疫沉淀，并进行了质谱分析以鉴定其相互作用伙伴。通过与 PLAC1 共转染和免疫沉淀直接测试相关蛋白的相互作用。在 PLAC1 的 ZP-N 结构域中引入突变来评估其在相互作用中的参与。我们提供的证据表明 Desmoglein-2 (DSG2)（膜相关桥粒复合物的一个组成部分）可直接与 PLAC1 相互作用。 ZP-N 结构域中半胱氨酸的突变破坏了 PLAC1 和 DSG-2 之间的相互作用。由于桥粒负责建立侧向细胞-细胞连接，因此我们认为与侧向连接蛋白复合物的直接相互作用可能涉及 PLAC1 对细胞-细胞相互作用的影响，从而影响胎盘的层结构。
X-linked PLAC1 is highly expressed in placenta during embryogenesis, and when ablated in mice, causes aberrant placental cell layer organization. It is also highly expressed in many types of cancer cell-lines. Although it has been shown that it promotes AKT phosphorylation in cancer cells, the exact mechanism by which it influences placental layer differentiation is unclear. To investigate the mechanism of action of PLAC1 we did cell fractionation and immunoprecipitation of the protein and Mass Spectrometry analysis to identify its interaction partners. The associated proteins were directly tested for interactions by co-transfection with PLAC1 and immunoprecipitation. Mutations in the ZP-N domain of PLAC1 were introduced to assess its involvement in the interactions. We provide evidence that Desmoglein-2 (DSG2), a component of the membrane-associated desmosomal complex, directly interacts with PLAC1. Mutations of cysteines in ZP-N domain disrupt the interaction between PLAC1 and DSG-2. Because desmosomes are responsible for establishing lateral cell-cell junctions, we suggest that direct interaction with the lateral junction protein complex may be implicated in the PLAC1 effects on cell-cell interactions, and thereby on the layer structure of the placenta.
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