Journal of cell science最新文献

Lipid membranes form the essential barriers that compartmentalize life, separating intracellular processes from the external environment. To maintain cellular function and viability, both the plasma membrane and internal organelle membranes undergo continuous compositional and functional remodeling in response to environmental fluctuations. Traditionally, glycerophospholipids have been primarily considered structural components of these membranes. However, their dynamic synthesis plays a crucial role in modulating membrane functions and, consequently, cellular adaptability. This Review discusses how cells orchestrate complex glycerophospholipid metabolism to adapt to diverse environmental challenges. By examining membrane adaptation to various changes, including temperature shifts, pH imbalances and nutrient availability, we propose that responsive alterations in glycerophospholipid synthesis act as a central metabolic hub. This hub influences overall cellular metabolism and regulatory networks. This Review highlights an often overlooked aspect of lipid biology: the pivotal role of glycerophospholipid metabolism in modulating cellular adaptability and resilience.

Studying how actin filaments are assembled into different subcellular structures can provide insights into both physiological processes and the mechanisms of disease. However, quantifying the size, abundance, and organization of different classes of actin structure from optical microscopy data remains a challenge. To address this, we developed a deep learning based Filamentous Actin Segmentation Tool (FAST) to accurately and efficiently segment and quantify different classes of actin structure from Phalloidin stained confocal microscopy images. We evaluated the performance of this tool to segment and quantify the abundance of different classes of actin structure in different cell lines and with dynamic changes in actin organization using lifeact-GFP during drug treatments. FAST enables quantification of different classes of actin structure from actin images alone, without the need for specific antibodies against proteins in different actin structures and hence can be a useful tool for researchers studying actin related pathways involved in cell motility, cancer metastasis, and drug development.

The production of engineered proteins in transgenic cells is widely used in research, medicine, and industry. However, conventional cell-based production systems still face challenges in cost, scalability, and biosafety. Here, we present a recombinant protein expression platform with simplified purification based on the photosynthetic unicellular red alga Cyanidioschyzon merolae, which can be cultivated under highly acidic conditions using only inorganic nutrients, air, water, and light. We first identified a promoter that drives high-level constitutive gene expression throughout the cell cycle, resulting in substantial mRNA accumulation in C. merolae. A stable transformant expressing His-tagged mVenus under the control of this promoter accumulated the recombinant protein to more than 1% of total soluble protein. The simple cellular architecture of C. merolae, including the absence of a cell wall, enables efficient protein extraction via a single freeze-thaw cycle, followed by purification using immobilized metal affinity chromatography (IMAC), yielding approximately 13.9 mg of functional recombinant protein per gram of total soluble protein. Owing to its low cost, scalability, operational simplicity, and minimal risk of contamination, this Cyanidioschyzon-based platform offers a practical and promising approach to recombinant protein production in a photosynthetic eukaryote.

The PRC2 complex tri-methylates histone 3 at lysine 27 (k27), a post translational modification that induces heterochromatin formation and transcriptional repression. Survivin is a nucleocytoplasmic shuttling protein that is kept out of the nucleus in clement conditions, but that accumulates there in times of stress and in certain specialised cells. While the cytoplasmic functions of survivin are well documented, there is comparatively less understanding of its roles within the nucleus. Here we investigated whether nuclear survivin can affect transcriptional programming. Using interaction analyses and qPCR we report that it binds to the enzymatic subunit of the polycomb repressor complex 2, EZH2 and H3k27Me3, and causes depression of its target genes in a variety of human cells.

The hair follicle cycles between anagen and telogen. During anagen, transit amplifying cells within the germinative matrix at the follicle bulb drive rapid proliferation for hair growth. This region exhibits some of the highest mitotic rates observed in any tissue, offering a rare opportunity to study mitosis in its native epithelial context, previously studied only in cultured cell lines. We applied volume electron microscopy to intact, chemically fixed hair follicles enabling exceptional ultrastructural preservation of the entire mini-organ. Morphometric analysis revealed stage-specific changes in chromosomal and organelle volume and spatial distribution, highlighting coordinated mitochondrial, vesicle, and endoplasmic reticulum roles, and enabled, to our knowledge, the first ultrastructure-based karyotype of ovine chromosomes. This work advances understanding of mitosis by resolving ultrastructure in a highly proliferative, spatially constrained epithelial microenvironment, demonstrating the power of serial block face scanning electron microscopy to bridge in vitro models and native tissue architecture.

Crosstalk between tumor microenvironmental factors, such as, extracellular matrix (ECM) stiffness and metabolic pathways, regulate cell invasive phenotype in cancer cells. ECM stiffening leads to the collapse of blood vessels leading to oxygen deprivation and nutrient stress. The individual and combined effect of these two factors on the mode of invasion of cancer cells remains poorly understood. Here we show that in breast cancer cells, glucose deprivation induces a switch from an energy demanding proteolytic mode of migration to an energy efficient non-proteolytic mode of migration. Energy demands met by OXPHOS, and nuclear softening sustain this mode of migration. We further show that the energy sensor AMPK mediates this switch through transcriptional activation of the mechanoresponsive actin crosslinking protein α-actinin-4. Collectively, our results demonstrate how AMPK fine-tunes mode of invasion under nutrient constraints by transcriptional activation of α-actinin-4.

A highly curved membrane region connecting the inner and the outer nuclear membrane serves as a platform where nucleoporins with one or more transmembrane domains promote anchoring of the nuclear pore complex to the nuclear envelope. In mammalian cells, three transmembrane nucleoporins, Nup210, POM121 and NDC1, are inserted at this site. Here, we characterize TMEM209, which had initially been identified as a protein concentrated at the nuclear envelope, as a fourth transmembrane nucleoporin. Proximity labeling revealed that TMEM209 occurs close to proteins of the inner nuclear membrane and to other nucleoporins. TMEM209 localized to the nuclear pore complex in immunofluorescence microscopy and biochemically interacted with Nup210 via a region containing its two transmembrane domains. TMEM209 depletion impaired cell growth and delayed entry into S, G2 and M phases of the cell cycle. Conversely, its overexpression specifically dissociated Nup210 from the nuclear envelope. Together, these findings establish TMEM209 as a novel transmembrane nucleoporin that cooperates with Nup210 in cell cycle progression and cell proliferation.

Epithelial tissues form protective barriers while supporting critical functions such as absorption and secretion. Their structural and functional integrity relies on adherens junctions, which coordinate migration and transmit forces between adjacent cells by connecting their actin cytoskeleton. In this study, we report the presence of an apical supracellular actin network in squamous epithelial cells. Using squamous carcinoma A431 cells as a model, we characterized this network composed of star-shaped actin structures interconnected by linear actin bundles that span multiple cells. We demonstrate that the network's formation and maintenance require actomyosin contractility and intact adherens junctions, while tight junctions seem dispensable. Furthermore, this network dynamically reorganizes as cells migrate and preferentially aligns with the direction of movement. This contractile structure generates mechanical tension that extends across the apical surface of multiple cells. Our findings suggest that this supracellular actin network functions as a long-range force transmission device in squamous cells, advancing our understanding of the biomechanical properties of epithelia.

Mitotic chromosome dimensions differ between species, and they differ between developmental stages within an organism. The physiological determinants of chromosome size remain poorly understood. Here, we investigate chromosome size determinants in the fission yeast Schizosaccharomyces pombe. Super-resolution microscopy and semi-automated measurements reveal that cell or nuclear volume in interphase, or the time spent in mitosis (both previously proposed chromosome size determinants), have little influence on resultant chromosome dimensions. Instead, levels of the chromosomal condensin complex affect chromosome size, with increasing condensin levels resulting in more compact, thinner and shorter, chromosomes. Our observations inform the understanding of how chromosome dimensions are controlled in an organism. They suggest that a chromosome-intrinsic mechanism sets chromosome size, more so than the environment in which chromosomes find themselves in.