Biology subjects

Meszaros, A.

Publications and source records attributed to Meszaros, A..

5 recordsLinked to original sources

bioRxiv2026

Multivalent ubiquitin recognition regulates multiple stages of Tau self-assembly

Liquid-liquid phase separation (LLPS) has emerged as an important intermediate in the pathological self-assembly of Tau, yet the molecular mechanisms that regulate this process remain incompletely understood. Although ubiquitin is a prominent component of pathological inclusions in tauopathies and other neurodegenerative diseases, its presence has largely been linked to targeting aberrant proteins for proteasomal or autophagic clearance. Here, we identify Tau as a ubiquitin-binding protein and demonstrate that multivalent, non-covalent ubiquitin recognition regulates multiple stages of Tau self-assembly. Biochemical, biophysical, structural, and computational analyses identified four ubiquitin-binding elements within the Tau microtubule-binding repeat region that engage the canonical hydrophobic patch of ubiquitin, providing a structural basis for multivalent recognition of mono- and poly-ubiquitin species. Functionally, mono- and poly-ubiquitin suppress Tau condensate formation while enhancing the liquid-like properties of condensates that persist. In contrast, mono-ubiquitin selectively enhances aggregation of the disease-linked Tau-P301L variant under conditions without detectable LLPS, demonstrating that ubiquitin exerts distinct effects depending on the molecular context and stage of Tau self-assembly. Together, these findings establish non-covalent ubiquitin recognition as a previously unrecognized mechanism regulating Tau phase behavior and aggregation. More broadly, they expand the role of ubiquitin beyond protein quality control, with ubiquitin architecture providing an additional layer of regulation over Tau condensate formation, dynamics, maturation, and aggregation.

biophysics↗

bioRxiv2026

Low-intensity ultrasound drives offline neuromodulation through passive membrane mechanisms in synaptically isolated hippocampal neurons

Low-intensity ultrasound alters neuronal excitability long after exposure ends, but the basis of this offline effect is unclear and most proposed mechanisms require synaptic receptors. We recorded from cultured mouse hippocampal neurons in whole-cell current clamp, before and 20 min after 1 min of 850 kHz continuous-wave ultrasound at 0.5 W/cm2 or sham, with synaptic transmission blocked throughout, each neuron re-patched. Sonicated neurons remained intact and firing, yet depolarized, with smaller action potentials and more noise. A passive-membrane fit showed reduced capacitance and a depolarized leak reversal potential in every sonicated cell, with a shortened time constant and no detectable change in input conductance, while sham cells showed no significant change. Changes in the time constant and reversal potential, both independent of membrane area, indicate a modification of the membrane itself rather than a loss of area. Brief ultrasound therefore leaves a lasting, receptor-independent imprint on passive membrane properties.

neuroscience↗

bioRxiv2026

Drivers of mosquito presence and abundance in urban and garden ponds in a European city

Mosquitoes in urban environments are considered unpleasant by citizens, and they can represent serious health risks as disease vectors. Invasive Aedes species are continuously spreading in Europe and have been increasingly reported from urban settlements. Some of these mosquito species have been associated with small artificial habitats. Therefore, their presence may also be expected in small plastic garden ponds, which are numerous in urban settings across many parts of Europe. Here, we aimed to determine whether urban waters host a high occurrence of mosquitoes and to identify the potential abiotic, biotic and landscape drivers of mosquito presence and abundance in urban ponds. We sampled 53 urban ponds in the city of Budapest (Hungary) of both natural and anthropogenic origin, and 40 garden ponds, which cover both highly urbanised areas and those with high green index in the suburbs. We collected data on macroinvertebrate communities, pond management, physico-chemical parameters, and pond characteristics (mainly morphology and vegetation cover) measured in situ. Two different mosquito detection techniques were used: dip-net sampling and eDNA. While only one invasive species (Aedes koreicus) was detected, occurring in a single pond, several other species were present, including potential malaria vectors increasingly reported from urban environments: the Anopheles maculipennis complex, An. claviger and An. plumbeus. Fish presence was negatively associated with both the presence and abundance of mosquitoes, regardless of pond type. Contrary to expectations, urbanisation did not play a major role in explaining mosquito presence or abundance. These results highlight the importance of local pond characteristics, and particularly the role of fish presence, in regulating mosquito populations in ponds in the urban landscape, although the broader ecological effects of fish on pond communities should also be considered.

ecology↗

bioRxiv2025

Expression and Purification of Full-Length hnRNPA2B1 for Biophysical Characterization of Liquid-Liquid Phase Separation

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is a multifunctional RNA-binding protein involved in RNA maturation and mRNA transport. It has recently been shown to undergo liquid-liquid phase separation (LLPS), contributing to the assembly of membraneless organelles. Moreover, dysregulation of LLPS is associated with the formation of pathogenic protein aggregates, in which hnRNPA2B1 is frequently found. Despite its biological and pathological relevance, studies on the full-length protein remain limited due to its intrinsically disordered, low-complexity domain, which renders hnRNPA2B1 highly aggregation-prone and difficult to purify. In this study, we report the successful expression and purification of full-length hnRNPA2B1 with high purity and minimal nucleic acid contamination. By optimizing buffer conditions, specifically ionic strength and pH, we maintain the protein in solution following cleavage of its solubility tag. Preliminary in vitro characterization under near-physiological conditions reveals that purified hnRNPA2B1 undergoes LLPS, forming dynamic liquid-like droplets that grow and mature into amorphous aggregates. Our approach provides a robust method for purifying hnRNPA2B1 suitable for LLPS and aggregation studies. This strategy may also be useful to purify other aggregation-prone, intrinsically disordered proteins.

biochemistry↗

bioRxiv2023

Menin regulates androgen receptor- and MLL-driven condensation, upsetting regulation of cellular AR-driven transcription.

Menin is a protein that is regulated via protein-protein interactions by different binding partners, such as mixed lineage leukemia protein (MLL) and androgen receptor (AR). We observed that menin-AR and menin-MLL interactions are regulated by concentration-dependent dimerization of menin, and its interaction with cancer-related AR. As a result of its oligomerization-dependent interaction with both AR and MLL, menin is recruited into AR-RNA and MLL-RNA condensates formed by liquid-liquid phase separation (LLPS), with different outcomes under AR-overexpression or MLL-overexpression conditions representing different cancer types. At high concentrations promoting menin dimerization, it inhibits MLL-RNA LLPS, while making AR-RNA condensates less dynamic, i.e., more gel-like. Regions of AR show both negative/positive cooperativity in menin binding. AR contains a specific menin-binding region (MBR) in its intrinsically disordered N-terminal domain (NTD), menin binding of which is inhibited by the adjacent DNA-binding domain (DBD), but facilitated by a hinge region located between its DBD and ligand-binding domain (LBD) as well as by N terminus of AR. Interestingly, the hinge region reduces the propensity of full-length AR to undergo LLPS in the presence of RNA, which is facilitated by an alternative hinge region present in the tumor-specific AR isoform, AR-v7. As both menin and MLL are recruited into AR-driven, functional cellular condensates aggravated in the case of AR-v7, we posit that the menin-AR-MLL system represents a fine-tuned condensate module of transcription regulation that is balanced toward the tumor-suppressor activity of menin. Our results suggest that this balance can be upset by prevalent oncogenic events, such as menin upregulation and/or AR-v7 overexpression, in cancer.

biochemistry↗