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1. Intracellular protein gradients serve a variety of functions, such as the establishment of cell polarity or to provide positional information for gene expression in developing embryos. Given that cell size in a population can vary considerably, for the protein gradients to work properly they often have to be scaled to the size of the cell. Here, we examine a model of protein gradient formation within a cell that relies on cytoplasmic diffusion and cortical transport of proteins toward a cell pole. We show that the shape of the protein gradient is determined solely by the cell geometry. Furthermore, we show that the length scale over which the protein concentration in the gradient varies is determined by the linear dimensions of the cell, independent of the diffusion constant or the transport speed. This gradient provides scale-invariant positional information within a cell, which can be used for assembly of intracellular structures whose size is scaled to the linear dimensions of the cell, such as the cytokinetic ring and actin cables in budding yeast cells.

   https://doi.org/10.7554/eLife.71365  

   Datta, Arnab; Ghosh, Sagnik; Kondev, Jane (March 2022, eLife)

   Intracellular protein gradients serve a variety of functions, such as the establishment of cell polarity or to provide positional information for gene expression in developing embryos. Given that cell size in a population can vary considerably, for the protein gradients to work properly they often have to be scaled to the size of the cell. Here, we examine a model of protein gradient formation within a cell that relies on cytoplasmic diffusion and cortical transport of proteins toward a cell pole. We show that the shape of the protein gradient is determined solely by the cell geometry. Furthermore, we show that the length scale over which the protein concentration in the gradient varies is determined by the linear dimensions of the cell, independent of the diffusion constant or the transport speed. This gradient provides scale-invariant positional information within a cell, which can be used for assembly of intracellular structures whose size is scaled to the linear dimensions of the cell, such as the cytokinetic ring and actin cables in budding yeast cells. 

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2. Contextual AI models for single-cell protein biology

   https://doi.org/10.1038/s41592-024-02341-3  

   Li, Michelle M; Huang, Yepeng; Sumathipala, Marissa; Liang, Man Qing; Valdeolivas, Alberto; Ananthakrishnan, Ashwin N; Liao, Katherine; Marbach, Daniel; Zitnik, Marinka (August 2024, Nature Methods)

   Abstract Understanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across biological contexts remains challenging for existing algorithms. Here we introduce PINNACLE, a geometric deep learning approach that generates context-aware protein representations. Leveraging a multiorgan single-cell atlas,PINNACLElearns on contextualized protein interaction networks to produce 394,760 protein representations from 156 cell type contexts across 24 tissues.PINNACLE’s embedding space reflects cellular and tissue organization, enabling zero-shot retrieval of the tissue hierarchy. Pretrained protein representations can be adapted for downstream tasks: enhancing 3D structure-based representations for resolving immuno-oncological protein interactions, and investigating drugs’ effects across cell types.PINNACLEoutperforms state-of-the-art models in nominating therapeutic targets for rheumatoid arthritis and inflammatory bowel diseases and pinpoints cell type contexts with higher predictive capability than context-free models.PINNACLE’s ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology. 

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3. Evidence of a novel silencing effect on transgenes in the Arabidopsis thaliana sperm cell

   https://doi.org/10.1093/plcell/koad219  

   Ohnishi, Yukinosuke; Kawashima, Tomokazu (August 2023, The Plant Cell)

   Abstract We encountered unexpected transgene silencing in Arabidopsis thaliana sperm cells; transgenes encoding proteins with no specific intracellular localization (cytoplasmic proteins) were silenced transcriptionally or posttranscriptionally. The mRNA of cytoplasmic protein transgenes tagged with a fluorescent protein gene was significantly reduced, resulting in undetectable fluorescent protein signals in the sperm cell. Silencing of the cytoplasmic protein transgenes in the sperm cell did not affect the expression of either its endogenous homologous genes or cotransformed transgenes encoding a protein with targeted intracellular localization. This transgene silencing in the sperm cell persisted in mutants of the major gene silencing machinery including DNA methylation. The incomprehensible, yet real, transgene silencing phenotypes occurring in the sperm cell could mislead the interpretation of experimental results in plant reproduction, and this Commentary calls attention to that risk and highlights details of this novel cytoplasmic protein transgene silencing. 

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4. Multiple domains of scaffold Tudor protein play nonredundant roles in Drosophila germline

   https://doi.org/10.26508/lsa.202503304  

   Tindell, Samuel J; Boeving, Alyssa G; Aebersold, Julia; Arkov, Alexey L (July 2025, Life Science Alliance)

   Scaffold proteins play crucial roles in subcellular organization and function. In many organisms, proteins with multiple Tudor domains are required for the assembly of membraneless RNA–protein organelles (germ granules) in germ cells. Tudor domains are protein–protein interaction modules which bind to methylated polypeptides.DrosophilaTudor protein contains 11 Tudor domains, which is the highest number known in a single protein. The role of each of these domains in germ cell formation has not been systematically tested, and it is not clear if some domains are functionally redundant. Using CRISPR methodology, we generated mutations in several uncharacterized Tudor domains and showed that they all caused defects in germ cell formation. Mutations in individual domains affected Tudor protein differently, causing reduction in protein levels and defects in subcellular localization and in the assembly of germ granules. Our data suggest that multiple domains of Tudor protein are all needed for efficient germ cell formation, highlighting the rational for keeping many Tudor domains in protein scaffolds of biomolecular condensates inDrosophilaand other organisms. 

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5. Multiple domains of scaffold Tudor protein play non-redundant roles in Drosophila germline

   https://doi.org/10.1101/2025.03.13.643173  

   Tindell, Samuel J; Boeving, Alyssa G; Aebersold, Julia; Arkov, Alexey L (March 2025, bioRxiv)

   Abstract Scaffold proteins play crucial roles in subcellular organization and function. In many organisms, proteins with multiple Tudor domains are required for the assembly of membraneless RNA-protein organelles (germ granules) in germ cells. Tudor domains are protein-protein interaction modules which bind to methylated polypeptides.DrosophilaTudor protein contains eleven Tudor domains, which is the highest number known in a single protein. The role of each of these domains in germ cell formation has not been systematically tested and it is not clear if some domains are functionally redundant. Using CRISPR methodology, we generated mutations in several uncharacterized Tudor domains and showed that they all caused defects in germ cell formation. Mutations in individual domains affected Tudor protein differently causing reduction in protein levels, defects in subcellular localization and in the assembly of germ granules. Our data suggest that multiple domains of Tudor protein are all needed for efficient germ cell formation highlighting the rational for keeping many Tudor domains in protein scaffolds of biomolecular condensates inDrosophilaand other organisms. 

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