TY - JOUR AU - Szabó, Anikó AU - Borkúti, Péter AU - Kovács, Zoltán AU - Kristó, Ildikó AU - Vilmos, Péter TI - Recent advances in nuclear actin research JF - NUCLEUS J2 - NUCLEUS-PHILA VL - 16 PY - 2025 IS - 1 PG - 22 SN - 1949-1034 DO - 10.1080/19491034.2025.2498643 UR - https://m2.mtmt.hu/api/publication/36200779 ID - 36200779 N1 - Funding Agency and Grant Number: NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program [20222.1.1-NL-2022-00008] Funding text: This work was supported by NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program, grant [20222.1.1-NL-2022-00008] (PV). AB - Actin was first observed in the nucleus more than sixty years ago but research on nuclear actin did not receive significant attention for the next forty years. It only started to accelerate around the year 2000, when the first convincing experimental data emerged indicating that actin participates in essential nuclear processes. Today, we know that actin is involved in transcription, replication, DNA repair, chromatin remodeling, and participates in the determination of nuclear shape and size. In this paper we review the results of the last five years of increasingly intensive research on nuclear actin, because on one hand, the field has expanded with several new directions during this time, and on the other hand, the enrichment of our picture of nuclear actin will certainly provide a more solid foundation and new impetus for its future investigation. LA - English DB - MTMT ER - TY - JOUR AU - Bence, Melinda AU - Jankovics, Ferenc AU - Kristó, Ildikó AU - Gyetvai, Akos AU - Vértessy, Beáta (Grolmuszné) AU - Erdélyi, Miklós TI - Direct interaction of Su(var)2-10 via the SIM-binding site of the Piwi protein is required for transposon silencing in Drosophila melanogaster JF - FEBS JOURNAL J2 - FEBS J VL - 291 PY - 2024 IS - 8 SP - 1759 EP - 1779 PG - 21 SN - 1742-464X DO - 10.1111/febs.17073 UR - https://m2.mtmt.hu/api/publication/34575637 ID - 34575637 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [K132384, PD124446]; Janos Bolyai Fellowship of Hungarian Academy of Sciences [BO/00599/17]; UNKP New National Excellence Program of the Ministry of Human Capacities of Hungary [UNKP-19-4-SZTE-5]; National Research, Development and Innovation Office (National Laboratory for Biotechnology) [2022-2.1.1-NL-2022-00008]; National Research, Development and Innovation Office [K135231, K146890, FK137867, VEKOP-2.3.2-16-2017-00013, NKP-2018-1.2.1-NKP-2018-00005]; Ministry for Innovation and Technology of Hungary from the National Research, Development and Innovation Fund; [TKP2021-EGA-02] AB - Nuclear Piwi/Piwi-interacting RNA complexes mediate co-transcriptional silencing of transposable elements by inducing local heterochromatin formation. In Drosophila, sumoylation plays an essential role in the assembly of the silencing complex; however, the molecular mechanism by which the sumoylation machinery is recruited to the transposon loci is poorly understood. Here, we show that the Drosophila E3 SUMO-ligase Su(var)2-10 directly binds to the Piwi protein. This interaction is mediated by the SUMO-interacting motif-like (SIM-like) structure in the C-terminal domain of Su(var)2-10. We demonstrated that the SIM-like structure binds to a special region found in the MID domain of the Piwi protein, the structure of which is highly similar to the SIM-binding pocket of SUMO proteins. Abrogation of the Su(var)2-10-binding surface of the Piwi protein resulted in transposon derepression in the ovary of adult flies. Based on our results, we propose a model in which the Piwi protein initiates local sumoylation in the silencing complex by recruiting Su(var)2-10 to the transposon loci. LA - English DB - MTMT ER - TY - JOUR AU - Borkúti, Péter AU - Kristó, Ildikó AU - Szabó, Anikó AU - Kovács, Zoltán AU - Vilmos, Péter TI - FERM domain-containing proteins are active components of the cell nucleus JF - LIFE SCIENCE ALLIANCE J2 - LIFE SCI ALLIANCE VL - 7 PY - 2024 IS - 4 PG - 15 SN - 2575-1077 DO - 10.26508/lsa.202302489 UR - https://m2.mtmt.hu/api/publication/34575638 ID - 34575638 N1 - Funding Agency and Grant Number: NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program [2022-2.1.1-NL-2022-00008] Funding text: This work was supported by NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program, grant 2022-2.1.1-NL-2022-00008 (to P Vilmos) . AB - The FERM domain is a conserved and widespread protein module that appeared in the common ancestor of amoebae, fungi, and animals, and is therefore now found in a wide variety of species. The primary function of the FERM domain is localizing to the plasma membrane through binding lipids and proteins of the membrane; thus, for a long time, FERM domain-containing proteins (FDCPs) were considered exclusively cytoskeletal. Although their role in the cytoplasm has been extensively studied, the recent discovery of the presence and importance of cytoskeletal proteins in the nucleus suggests that FDCPs might also play an important role in nuclear function. In this review, we collected data on their nuclear localization, transport, and possible functions, which are still scattered throughout the literature, with special regard to the role of the FERM domain in these processes. With this, we would like to draw attention to the exciting, new dimension of the role of FDCPs, their nuclear activity, which could be an interesting novel direction for future research. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Zoltán AU - Bajusz, Csaba AU - Szabó, Anikó AU - Borkúti, Péter AU - Vedelek, Balázs AU - Benke, Reka AU - Lipinszki, Zoltán AU - Kristó, Ildikó AU - Vilmos, Péter TI - A bipartite NLS motif mediates the nuclear import of Drosophila moesin JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 12 PY - 2024 PG - 14 SN - 2296-634X DO - 10.3389/fcell.2024.1206067 UR - https://m2.mtmt.hu/api/publication/34743202 ID - 34743202 N1 - Funding Agency and Grant Number: NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program [PD127968, LP2017-7/2017]; Hungarian Academy of Sciences Lendulet Grant; [2022-2.1.1-NL-2022-00008] Funding text: This work was supported by NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program, grant 2022-2.1.1-NL-2022-00008 (PV), and PD127968 (IK), and the Hungarian Academy of Sciences Lendulet Grant LP2017-7/2017 (ZL). AB - The ERM protein family, which consists of three closely related proteins in vertebrates, ezrin, radixin, and moesin (ERM), is an ancient and important group of cytoplasmic actin-binding and organizing proteins. With their FERM domain, ERMs bind various transmembrane proteins and anchor them to the actin cortex through their C-terminal F-actin binding domain, thus they are major regulators of actin dynamics in the cell. ERMs participate in many fundamental cellular processes, such as phagocytosis, microvilli formation, T-cell activation and tumor metastasis. We have previously shown that, besides its cytoplasmic activities, the single ERM protein of Drosophila melanogaster, moesin, is also present in the cell nucleus, where it participates in gene expression and mRNA export. Here we study the mechanism by which moesin enters the nucleus. We show that the nuclear import of moesin is an NLS-mediated, active process. The nuclear localization sequence of the moesin protein is an evolutionarily highly conserved, conventional bipartite motif located on the surface of the FERM domain. Our experiments also reveal that the nuclear import of moesin does not require PIP2 binding or protein activation, and occurs in monomeric form. We propose, that the balance between the phosphorylated and non-phosphorylated protein pools determines the degree of nuclear import of moesin. LA - English DB - MTMT ER - TY - JOUR AU - Kristó, Ildikó AU - Kovács, Zoltán AU - Szabó, Anikó AU - Borkúti, Péter AU - Gráf, Alexandra AU - Sánta, Ádám Tamás AU - Pettkó-Szandtner, Aladár AU - Ábrahám, Edit AU - Honti, Viktor AU - Lipinszki, Zoltán AU - Vilmos, Péter TI - Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus JF - OPEN BIOLOGY J2 - OPEN BIOL VL - 14 PY - 2024 IS - 10 PG - 20 SN - 2046-2441 DO - 10.1098/rsob.240110 UR - https://m2.mtmt.hu/api/publication/35464318 ID - 35464318 N1 - Funding Agency and Grant Number: National Laboratory for Biotechnology [2P40OD010949]; NIH; Carnegie Institution of Washington Funding text: The authors are grateful for the Drosophila Genomics Resource Center (DGRC), supported by NIH grant 2P40OD010949, for providing the cDNA clones. Permission for the Drosophila Gateway expression vectors (pAWG, pAWH, pAWF) was obtained from The Carnegie Institution of Washington. AB - The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding. LA - English DB - MTMT ER - TY - JOUR AU - Kharrat, Bayan AU - Gábor, Erika AU - Virag, Nikolett AU - Sinka, Rita AU - Jankovics, Ferenc AU - Kristó, Ildikó AU - Vilmos, Péter AU - Csordás, Gábor AU - Honti, Viktor TI - Dual role for Headcase in hemocyte progenitor fate determination in Drosophila melanogaster JF - PLOS GENETICS J2 - PLOS GENET VL - 20 PY - 2024 IS - 10 PG - 25 SN - 1553-7390 DO - 10.1371/journal.pgen.1011448 UR - https://m2.mtmt.hu/api/publication/35619928 ID - 35619928 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [OTKA K-131484]; National Laboratory of Biotechnology [2022-2.1.1-NL-2022-00008] Funding text: This work was supported by the National Research, Development and Innovation Office OTKA K-131484 (VH) and the 2022-2.1.1-NL-2022-00008 (National Laboratory of Biotechnology) grants. BK received a salary from the 2022-2.1.1-NL-2022-00008 (National Laboratory of Biotechnology) grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AB - The hematopoietic organ of the Drosophila larva, the lymph gland, is a simplified representation of mammalian hematopoietic compartments, with the presence of hemocyte progenitors in the medullary zone (MZ), differentiated hemocytes in the cortical zone (CZ), and a hematopoietic niche called the posterior signaling centre (PSC) that orchestrates progenitor differentiation. Our previous work has demonstrated that the imaginal cell factor Headcase (Hdc, Heca) is required in the hematopoietic niche to control the differentiation of hemocyte progenitors. However, the downstream mechanisms of Hdc-mediated hematopoietic control remained unknown. Here we show that Hdc exerts this function by negatively regulating the insulin/mTOR signaling in the niche. When Hdc is depleted in the PSC, the overactivation of this pathway triggers reactive oxygen species (ROS) accumulation and, in turn, the differentiation of effector lamellocytes non-cell-autonomously. Although overactivation of insulin/mTOR signaling normally leads to an increase in the size of the hematopoietic niche, this effect is concealed by cell death caused by hdc loss-of-function. Moreover, we describe here that hdc silencing in progenitors causes cell-autonomous ROS elevation and JNK pathway activation, resulting in decreased MZ size and differentiation of lamellocytes. Similarly to the PSC niche, knocking down hdc in the MZ also leads to caspase activation. Notably, depleting Hdc in the progenitors triggers proliferation, an opposing effect to what is observed in the niche. These findings further our understanding of how progenitor maintenance in the larval lymph gland is controlled autonomously and non-cell-autonomously, and point towards new mechanisms potentially regulating HSC maintenance across vertebrates. LA - English DB - MTMT ER - TY - JOUR AU - Kristó, Ildikó AU - Borkúti, Péter AU - Kovács, Zoltán AU - Szabó, Anikó AU - Szikora, Szilárd AU - Vilmos, Péter TI - Detection of Actin in Nuclear Protein Fraction Isolated from Adult Drosophila Ovary JF - METHODS IN MOLECULAR BIOLOGY J2 - METHODS MOL BIOL VL - 2626 PY - 2023 SP - 353 EP - 364 PG - 12 SN - 1064-3745 DO - 10.1007/978-1-0716-2970-3_19 UR - https://m2.mtmt.hu/api/publication/34600475 ID - 34600475 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Anikó AU - Borkúti, Péter AU - Kovács, Zoltán AU - Kristó, Ildikó AU - Abonyi, Csilla AU - Vilmos, Péter TI - Measuring Transposable Element Activity in Adult Drosophila Ovaries JF - METHODS IN MOLECULAR BIOLOGY J2 - METHODS MOL BIOL VL - 2626 PY - 2023 SP - 309 EP - 321 PG - 13 SN - 1064-3745 DO - 10.1007/978-1-0716-2970-3_16 UR - https://m2.mtmt.hu/api/publication/34600487 ID - 34600487 LA - English DB - MTMT ER - TY - JOUR AU - Borkúti, Péter AU - Kristó, Ildikó AU - Szabó, Anikó AU - Bajusz, Csaba AU - Kovács, Zoltán AU - Réthi-Nagy, Zsuzsánna AU - Lipinszki, Zoltán AU - Lukacsovich, Tamas AU - Bogdan, Sven AU - Vilmos, Péter TI - Parallel import mechanisms ensure the robust nuclear localization of actin in Drosophila JF - FRONTIERS IN MOLECULAR BIOSCIENCES J2 - FRONT MOL BIOSCI VL - 9 PY - 2022 PG - 16 SN - 2296-889X DO - 10.3389/fmolb.2022.963635 UR - https://m2.mtmt.hu/api/publication/33133586 ID - 33133586 N1 - Funding Agency and Grant Number: NKFIH (National Research, Development and Innovation Office); Dr. Rollin D. Hotchkiss Foundation [NKFIH-871-3/2020, PD127968]; Hungarian Academy of Sciences Lenduelet Grant; [LP2017-7/2017] Funding text: This work was supported by NKFIH (National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program, grant NKFIH-871-3/2020 (PV), and PD127968 (IK), the Dr. Rollin D. Hotchkiss Foundation (PB), and the Hungarian Academy of Sciences Lenduelet Grant LP2017-7/2017 (ZL). AB - Actin, as an ancient and fundamental protein, participates in various cytoplasmic as well as nuclear functions in eukaryotic cells. 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. 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. 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. 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. 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. We found that, individually, none of the above mentioned manipulations led to a notable reduction in nuclear actin levels and thus, fully rescued lethality. 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. 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. LA - English DB - MTMT ER - TY - JOUR AU - Bajusz, Csaba AU - Kristó, Ildikó AU - Abonyi, Csilla AU - Venit, Tomáš AU - Vedelek, Viktor AU - Lukácsovich, Tamás AU - Farkas, Attila AU - Borkúti, Péter AU - Kovács, Zoltán AU - Bajusz, Izabella AU - Marton, Annamária AU - Vizler, Csaba AU - Lipinszki, Zoltán AU - Sinka, Rita AU - Percipalle, Piergiorgio AU - Vilmos, Péter TI - The nuclear activity of the actin‐binding Moesin protein is necessary for gene expression in Drosophila JF - FEBS JOURNAL J2 - FEBS J VL - 288 PY - 2021 IS - 16 SP - 4812 EP - 4832 PG - 21 SN - 1742-464X DO - 10.1111/febs.15779 UR - https://m2.mtmt.hu/api/publication/31909117 ID - 31909117 N1 - Eötvös Loránd Research Network (ELKH), Biological Research Centre, Szeged, Hungary Doctoral School of Biology, University of Szeged, Hungary Department of Genetics, University of Szeged, Hungary Doctoral School of Multidisciplinary Medical Science, University of Szeged, Hungary Lendület Laboratory of Cell Cycle Regulation, ELKH, Biological Research Centre, Szeged, Hungary AB - Ezrin–Radixin–Moesin (ERM) proteins play an essential role in the cytoplasm by cross‐linking actin filaments with plasma membrane proteins. Research has identified the nuclear localization of ERMs, as well as the involvement of a single Drosophila ERM protein, Moesin, in nuclear mRNA exports. However, the question of how important the nuclear activity of ERM proteins are for the life of an organism has so far not been explored. Here, we present the first attempt to reveal the in vivo relevance of nuclear localization of Moesin in Drosophila. With the help of a nuclear export signal, we decreased the amount of Moesin in the nuclei of the animals. Furthermore, we observed various developmental defects, demonstrating the importance of ERM function in the nucleus for the first time. Transcriptome analysis of the mutant flies revealed that the lack of nuclear Moesin function leads to expression changes in nearly 700 genes, among them heat‐shock genes. This result together with additional findings revealed that in Drosophila the expression of protein chaperones requires the nuclear functions of Moesin.DatabaseGEO accession number: GSE155778. LA - English DB - MTMT ER -