The role of nuclear spectrins in actin-dependent nuclear expansion and reorganization at mitosis

核血影蛋白在肌动蛋白依赖性核扩张和有丝分裂重组中的作用

• 批准号: 469191306
• 负责人: Professor Dr. Robert Grosse
• 金额: --
• 依托单位: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/469191306?language=en
• 关键词: role; nuclear; spectrins; actin; dependent

The actin cytoskeleton fulfils numerous cellular tasks to regulate cell shape and architecture, adhesion and contractility, transport and trafficking, or protrusions and polarity to name a few. Importantly, it has now become clear that a dynamic actin cytoskeleton also operates inside the mammalian cell nucleus. We could previously show that nuclear actin filament assembly functions during Serum-Response-Factor (SRF) transcription, during receptor-mediated rapid signaling to chromatin as well as during cell division in order to promote nuclear expansion and to reorganize daughter cell chromatin. However, many of the molecular factors and mechanisms during these processes are still poorly understood. Here we aim to analyse the role of non-erythrocytic spectrins during nuclear expansion and reorganization at mitotic exit. With the use of genome editing, biochemistry, high-resolution live cell imaging and atomic force microscopy we will investigate the impact of nuclear spectrin for nuclear actin dynamics as well as nuclear expansion and mechanical elasticity during cell division. These studies shall help to elucidate key mechanisms and to identify signaling components that underlie nuclear reorganization after mitosis essential for genome integrity and maintenance, which are frequently deregulated in cancer.

肌动蛋白细胞骨架完成许多细胞任务，以调节细胞形状和结构、粘附性和收缩性、运输和运输，或突起和极性，仅举几例。重要的是，现在已经清楚的是，动态肌动蛋白细胞骨架也在哺乳动物细胞核内运作。我们以前可以表明，核肌动蛋白丝组装在血清反应因子（SRF）转录过程中的功能，在受体介导的快速信号传递到染色质以及在细胞分裂过程中，以促进核扩张和重组子细胞染色质。然而，这些过程中的许多分子因素和机制仍然知之甚少。在这里，我们的目的是分析的作用，非红细胞血影蛋白在核扩张和重组在有丝分裂出口。通过使用基因组编辑，生物化学，高分辨率活细胞成像和原子力显微镜，我们将研究核血影蛋白对核肌动蛋白动力学以及细胞分裂过程中核扩张和机械弹性的影响。这些研究将有助于阐明关键机制，并确定有丝分裂后核重组的信号传导成分，这些成分对基因组的完整性和维持至关重要，而这些成分在癌症中经常被解除管制。