The role of WH2 domains in nuclear gene expression and actin nucleation

Beside its prominent role in cytoplasmic F-actin formation, actin nucleation also affects processes within the cell nucleus, such as gene expression through SRF and its coactivator MAL/MRTF. However, the precise connection between the nucleation promoting factors (NPFs), nuclear actin and MAL/SRF is unclear. The aim of this proposal is to elucidate the role of WH2-domains and -NPFs in nuclear processes, i.e. MAL/SRF-mediated transcription and formation of nuclear actin polymers. We will analyse the WH2-MAL competition by biochemical experiments and in living cells by imaging. Using both candidate approaches and unbiased screening, we will attempt to identify the critical WH2-containing NPFs.