More Like this

1. Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

   https://doi.org/10.7554/eLife.76075  

   Lemière, Joël; Real-Calderon, Paula; Holt, Liam J; Fai, Thomas G; Chang, Fred (July 2022, eLife)

   The size of the nucleus scales robustly with cell size so that the nuclear-to-cell volume ratio (N/C ratio) is maintained during cell growth in many cell types. The mechanism responsible for this scaling remains mysterious. Previous studies have established that the N/C ratio is not determined by DNA amount but is instead influenced by factors such as nuclear envelope mechanics and nuclear transport. Here, we developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in the fission yeast Schizosaccharomyces pombe . This model posits that the N/C ratio is determined by the numbers of macromolecules in the nucleoplasm and cytoplasm. Osmotic shift experiments showed that the fission yeast nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces. Inhibition of nuclear export caused accumulation of macromolecules in the nucleoplasm, leading to nuclear swelling. We further demonstrated that the N/C ratio is maintained by a homeostasis mechanism based upon synthesis of macromolecules during growth. These studies demonstrate the functions of colloid osmotic pressure in intracellular organization and size control. 

   more » « less
2. A nuclear import pathway exploited by pathogenic noncoding RNAs

   https://doi.org/10.1093/plcell/koac210  

   Ma, Junfei; Dissanayaka Mudiyanselage, Shachinthaka D.; Park, Woong June; Wang, Mo; Takeda, Ryuta; Liu, Bin; Wang, Ying (July 2022, The Plant Cell)

   Abstract The prevailing view of intracellular RNA trafficking in eukaryotic cells is that RNAs transcribed in the nucleus either stay in the nucleus or cross the nuclear envelope, entering the cytoplasm for function. However, emerging evidence illustrates that numerous functional RNAs move in the reverse direction, from the cytoplasm to the nucleus. The mechanism underlying RNA nuclear import has not been well elucidated. Viroids are single-stranded circular noncoding RNAs that infect plants. Using Nicotiana benthamiana, tomato (Solanum lycopersicum), and nuclear-replicating viroids as a model, we showed that cellular IMPORTIN ALPHA-4 (IMPa-4) is likely involved in viroid RNA nuclear import, empirically supporting the involvement of Importin-based cellular pathway in RNA nuclear import. We also confirmed the involvement of a cellular protein (viroid RNA-binding protein 1 [VIRP1]) that binds both IMPa-4 and viroids. Moreover, a conserved C-loop in nuclear-replicating viroids serves as a key signal for nuclear import. Disrupting C-loop impairs VIRP1 binding, viroid nuclear accumulation, and infectivity. Further, C-loop exists in a subviral satellite noncoding RNA that relies on VIRP1 for nuclear import. These results advance our understanding of subviral RNA infection and the regulation of RNA nuclear import. 

   more » « less
3. Working a second job: Cell adhesion proteins that moonlight in the nucleus

   https://doi.org/10.3389/fcell.2023.1163553  

   Haage, Amanda; Dhasarathy, Archana (April 2023, Frontiers in Cell and Developmental Biology)

   Cells are adept at sensing changes in their environment, transmitting signals internally to coordinate responses to external stimuli, and thereby influencing adaptive changes in cell states and behavior. Often, this response involves modulation of gene expression in the nucleus, which is seen largely as a physically separated process from the rest of the cell. Mechanosensing, whereby a cell senses physical stimuli, and integrates and converts these inputs into downstream responses including signaling cascades and gene regulatory changes, involves the participation of several macromolecular structures. Of note, the extracellular matrix (ECM) and its constituent macromolecules comprise an essential part of the cellular microenvironment, allowing cells to interact with each other, and providing both structural and biochemical stimuli sensed by adhesion transmembrane receptors. This highway of information between the ECM, cell adhesion proteins, and the cytoskeleton regulates cellular behavior, the disruption of which results in disease. Emerging evidence suggests a more direct role for some of these adhesion proteins in chromatin structure and gene regulation, RNA maturation and other non-canonical functions. While many of these discoveries were previously limited to observations of cytoplasmic-nuclear transport, recent advances in microscopy, and biochemical, proteomic and genomic technologies have begun to significantly enhance our understanding of the impact of nuclear localization of these proteins. This review will briefly cover known cell adhesion proteins that migrate to the nucleus, and their downstream functions. We will outline recent advances in this very exciting yet still emerging field, with impact ranging from basic biology to disease states like cancer. 

   more » « less
4. The Driving Force: Nuclear Mechanotransduction in Cellular Function, Fate, and Disease

   https://doi.org/10.1146/annurev-bioeng-060418-052139  

   Maurer, Melanie; Lammerding, Jan (June 2019, Annual Review of Biomedical Engineering)

   Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered. 

   more » « less
5. Nanomaterials for Protein Delivery in Anticancer Applications

   https://doi.org/10.3390/pharmaceutics13020155  

   Yau, Anne; Lee, Jinhyung; Chen, Yupeng (February 2021, Pharmaceutics)

   null (Ed.)

   Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as proteins, peptides, and nucleic acids. Among them, proteins have shown a series of advantages and potential in various therapeutic applications, such as introducing therapeutic proteins due to genetic defects, or used as nanocarriers for anticancer agents to decelerate tumor growth or control metastasis. This review discusses the existing nanoparticle delivery systems, introducing design strategies, advantages of using each system, and possible limitations. Moreover, we will examine the intracellular delivery of different protein therapeutics, such as antibodies, antigens, and gene editing proteins into the host cells to achieve anticancer effects and cancer vaccines. Finally, we explore the current applications of protein delivery in anticancer treatments. 

   more » « less