Plakophilin 3 phosphorylation by ribosomal S6 kinases supports desmosome assembly
Plakophilin 3 phosphorylation by ribosomal S6 kinases supports desmosome assembly
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DOI：
10.1242/jcs.238295
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发表时间：
2020-04-01
影响因子：
4
通讯作者：
Hatzfeld, Mechthild
中科院分区：
文献类型：
--
作者：
Mueller, Lisa;Rietscher, Katrin;Hatzfeld, Mechthild
桥粒重塑对表皮再生、分化和创伤愈合至关重要。它是通过调整组成蛋白的组成和翻译后修饰介导的。我们先前已经证明，在小鼠基底上角化细胞，plakophilin（PKP）1介导的强粘附，这是负调控的胰岛素样生长因子1（IGF 1）信号。PKP3对表皮粘附的重要性尚未完全了解。在这里，我们确定了表皮生长因子（EGF），而不是IGF1，在PKP3招聘质膜信号，以促进桥粒组装的主要作用。我们发现，核糖体S6激酶（RSK）与PKP3相关并使其磷酸化，从而促进PKP3与EGF受体下游的桥粒相关。RSK的敲除以及PKP3中RSK磷酸化位点的突变干扰了桥粒的形成、成熟和粘附。我们的研究结果表明，不同的生长因子在控制桥粒的粘附性能，通过在上下文依赖的方式调制PKPs的协调行动。
Desmosome remodeling is crucial for epidermal regeneration, differentiation and wound healing. It is mediated by adapting the composition, and by post-translational modifications, of constituent proteins. We have previously demonstrated in mouse suprabasal keratinocytes that plakophilin (PKP) 1 mediates strong adhesion, which is negatively regulated by insulin-like growth factor 1 (IGF1) signaling. The importance of PKP3 for epidermal adhesion is incompletely understood. Here, we identify a major role of epidermal growth factor (EGF), but not IGF1, signaling in PKP3 recruitment to the plasma membrane to facilitate desmosome assembly. We find that ribosomal S6 kinases (RSKs) associate with and phosphorylate PKP3, which promotes PKP3 association with desmosomes downstream of the EGF receptor. Knockdown of RSKs as well as mutation of an RSK phosphorylation site in PKP3 interfered with desmosome formation, maturation and adhesion. Our findings implicate a coordinate action of distinct growth factors in the control of adhesive properties of desmosomes through modulation of PKPs in a context-dependent manner.