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

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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.