In addition, nuclear microfilament-associated motor proteins as well as branching and severing factors, all of which are eukaryotic developments of the microfilament system, are also present in the cell nucleus ( Bajusz et al., 2018). It is now clear, that in the nucleus of eukaryotic cells functionally active monomers, filament formation and movement of chromatin represent an ancient actin world ( Moore and Vartiainen 2017 Plessner and Grosse, 2019). Since its discovery, eukaryotic actin had been considered to perform its manifold functions exclusively in the cytoplasm, but recent recognition of the existence of prokaryotic actin-like proteins and nuclear actin in eukaryotes have opened new perspectives on the field. Supporting this, we identified novel nuclear importins specific to actin, which sheds light on the mechanism behind the robustness of nuclear localization of actin, and supports the idea of essentiality of its nuclear functions. However, the NES tagging of actin, together with the knock out of its importin, significantly reduced the amount of nuclear actin and induced lethality, confirming that the presence of actin in the nucleus is essential, and thereby, over-secured. We found that, individually, none of the above mentioned manipulations led to a notable reduction in nuclear actin levels and thus, fully rescued lethality. We also disrupted the SUMOylation site of actin, suggested earlier to be responsible for nuclear retention, and eliminated the activity of the single nuclear import factor dedicated to actin. For this aim, we generated a genetic system in Drosophila, in which we rescued the lethal phenotype of the null mutation of the Actin5C gene with transgenes that express different derivatives of actin, including a Nuclear Export Signal (NES)-tagged isoform which ensures forced nuclear export of the protein. In our work, we tested the robustness of the nuclear import of actin, and investigated whether the perturbations of nuclear localization affect the viability of the whole organism. However, today only a single nuclear import and a single nuclear export pathway is known which maintain the dynamic balance between cytoplasmic and nuclear actin pools. Based on its manifold tasks in the nucleus, it is a reasonable assumption that the nuclear presence of actin is essential for the cell, and consequently, its nuclear localization is ensured by a robust system. 5Department of Molecular Cell Physiology, Institute of Physiology and Pathophysiology, Philipps-University, Marburg, GermanyĪctin, as an ancient and fundamental protein, participates in various cytoplasmic as well as nuclear functions in eukaryotic cells.4Brain Research Institute, University of Zürich, Zürich, Switzerland.3Biological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, Eötvös Loránd Research Network (ELKH), Szeged, Hungary.2Doctoral School of Multidisciplinary Medical Science, University of Szeged, Szeged, Hungary.1Eötvös Loránd Research Network (ELKH), Biological Research Centre, Szeged, Hungary.Péter Borkúti 1,2, Ildikó Kristó 1, Anikó Szabó 1, Csaba Bajusz 1 †, Zoltán Kovács 1,2, Zsuzsánna Réthi-Nagy 3, Zoltán Lipinszki 3, Tamás Lukácsovich 4, Sven Bogdan 5 and Péter Vilmos 1*

Front mission 2089 import review