Regulation of plakophilin1's dual function in translation and desmosome organization

plakophilin1 在翻译和桥粒组织中双重功能的调节

• 批准号: 194474942
• 负责人: Professorin Dr. Mechthild Hatzfeld
• 金额: --
• 依托单位: Arbeitsgruppe Pathobiochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194474942?language=en
• 关键词: Regulation; plakophilin1; dual; function; translation

Plakophilin 1 is a member of the armadillo-family of cell contact proteins that has an essential function in regulating desmosomal adhesion. Due to its considerable cytoplasmic and nuclear pool it has been hypothesized that plakophilins may have a signaling function similar to that of β-catenin. We have recently demonstrated that plakophilin 1 stimulates translation in vivo and in vitro through direct interaction with the eukaryotic translation initiation factor eIF4A1. Plakophilin 1 is part of the cap-binding eIF4F complex and promotes eIF4A1 and eIF4B recruitment into the cap-binding complex thereby stimulating translation. This correlates with an increase in proliferation and cell size. In the proposed project, we aim to characterize how the balance between the plakophilin 1-desmosomal and the cytoplasmic pool is regulated in vivo and how this affects intercellular adhesion, translation and proliferation. Preliminary evidence supports a role of plakophilin 1-phosphorylation by ribosomal S6 kinase (S6K) and AKT kinases. This will be characterized in detail and the physiological relevance will be investigated.

Plakophilin 1是犰狳家族细胞接触蛋白的一员，在调节桥粒黏附中具有重要功能。由于其大量的细胞质和核池，人们假设嗜血小板蛋白可能具有类似于β-连环蛋白的信号功能。我们最近已经证明嗜铂蛋白1通过与真核生物翻译起始因子eIF4A1的直接相互作用刺激体内和体外的翻译。嗜plakophil1是帽结合eIF4F复合体的一部分，促进eIF4A1和eIF4B招募到帽结合复合体中，从而刺激翻译。这与增殖和细胞大小的增加有关。在这个项目中，我们的目标是描述嗜血小板1-桥粒和细胞质池之间的平衡是如何在体内调节的，以及这是如何影响细胞间的粘附、翻译和增殖的。初步证据支持嗜血小板蛋白1磷酸化在核糖体S6激酶（S6K）和AKT激酶中的作用。这将被详细描述，生理相关性将被调查。

项目成果

Insulin signaling via Akt2 switches plakophilin 1 function from stabilizing cell adhesion to promoting cell proliferation

• DOI: 10.1242/jcs.118992
• 发表时间: 2013-04-15
• 期刊: JOURNAL OF CELL SCIENCE
• 影响因子: 4
• 作者: Wolf, Annika;Rietscher, Katrin;Hatzfeld, Mechthild
• 通讯作者: Hatzfeld, Mechthild