Biology subjects

Keuenhof, K.

Publications and source records attributed to Keuenhof, K..

3 recordsLinked to original sources

bioRxiv2026

The chaperone Jjj2 regulates nucleoporin condensation in budding yeast

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport through a selective permeability barrier established by nucleoporins (Nups) that contain intrinsically disordered phenylalanine-glycine (FG) repeats. Due to these domains, FG-Nups are prone to condensation, with a potential to transition into insoluble aggregates. How cells keep FG-Nups in a soluble, functional state during NPC assembly and within the native NPC remains poorly understood. Here, we identify the uncharacterized yeast J-domain protein Jjj2 as a Nup chaperone. Disrupting Jjj2 function or its interaction with Hsp70 chaperones triggers the accumulation of newly synthesized Nups in cytoplasmic condensates. Conversely, Jjj2 overexpression suppresses Nup condensation but also disrupts the NPC permeability barrier and is highly toxic. Overall, our data show that Jjj2, in concert with Hsp70, controls Nup phase state. This activity must be tightly regulated; while Jjj2 prevents condensation of newly produced Nups, its overactivity compromises nucleocytoplasmic compartmentalization.

cell biology↗

bioRxiv2025

Direct binding of arsenicals to nuclear transport factors disrupts nucleocytoplasmic transport

Human exposure to arsenicals is associated with devastating diseases such as cancer and neurodegeneration. At the same time, arsenic-based drugs are used as therapeutic agents. The ability of arsenic to directly bind to proteins is correlated with its toxic and therapeutic effects highlighting the importance of elucidating arsenic-protein interactions. In this study, we took a proteomic approach and identified 174 proteins that bind to arsenic in Saccharomyces cerevisiae. Proteins involved in nucleocytoplasmic transport were markedly enriched among the arsenic-binding proteins, and we demonstrate that arsenic-binding to nuclear import factors results in their relocation from the nuclear envelope and subsequent aggregation in the cytosol. Similarly, nuclear pore proteins that make up the nuclear pore complex mislocalized and aggregated in arsenic-exposed cells. Consequently, arsenic was shown to inhibit nuclear protein import and export. We propose a model in which arsenic-binding to nuclear transport factors leads to their mislocalization and aggregation, which disrupts nucleocytoplasmic transport and causes arsenic sensitivity.

cell biology↗

bioRxiv2021

Large Organellar Changes occur during Mild Heat Shock in Yeast

When the temperature is increased, the heat shock response is activated to protect the cellular environment. The transcriptomics and proteomics of this process are intensively studied, while information about how the cell responds structurally to heat stress is mostly lacking. Here, Saccharomyces cerevisiae were subjected to a mild continuous heat shock and intermittently cryo-immobilized for electron microscopy. Through measuring changes in all distinguishable organelle numbers, sizes, and morphologies in over 2400 electron micrographs a major restructuring of the cells internal architecture during the progressive heat shock was revealed. The cell grew larger but most organelles within it expanded even more. Organelles responded to heat shock at different times, both in terms of size and number, and adaptations of certain organelles morphology were observed. Multivesicular bodies grew to almost 170% in size, indicating a previously unknown involvement in the heat shock response. A previously undescribed electron translucent structure accumulated close to the plasma membrane during the entire time course. This all-encompassing approach provides a detailed chronological progression of organelle adaptation throughout the cellular stress response. Summary statementExposure to mild heat shock leads to large quantifiable changes in the cellular ultrastructure of yeast, shows involvement of MVBs in the heat shock response and the apparition of novel structures.

cell biology↗