Regulation and function of nuclear actin polymerization

• Applicant: Professor Dr. Robert Grosse
• Subject Area: Pharmacology ; Cell Biology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271359746

Signal-regulated nuclear actin polymerization is just beginning to emerge as a principal cellular process; however, underlying mechanisms and functional consequences remain poorly understood. We recently discovered serum-stimulated nuclear actin network assembly in intact mammalian cells. We identified the formins mDia1/2 as the responsible actin nucleation factors and demonstrated a direct mechanistic link between nuclear actin filament formation and SRF transcriptional activity. Nevertheless, whether there is a function of nuclear actin assembly during very general and physiological cellular processes remains unclear. It is the aim of this proposal to investigate nuclear actin polymerization in two fundamental cellular mechanisms: (i) we currently observe that nuclear actin polymerization occurs during extracellular matrix interactions, which appear to be mediated by integrin signaling and the nucleoskeleton, (ii) interestingly, our ongoing studies further reveal that a striking nuclear actin network forms in a highly defined manner during cell division at the end of mitosis indicative for a role in chromatin reorganization. We therefore plan to define and unravel the molecular mechanisms underlying nuclear actin polymerization triggered by mechanotransduction as well as by mitosis. These studies shall help in identifying novel concepts and promising pharmacological drug targets to interfere with malignant cell proliferation and adhesion.

• DFG Programme: Research Grants