Akihiro Kusumi , Taka A. Tsunoyama , Kenichi G.N. Suzuki , Takahiro K. Fujiwara , Amine Aladag
{"title":"Transient, nano-scale, liquid-like molecular assemblies coming of age","authors":"Akihiro Kusumi , Taka A. Tsunoyama , Kenichi G.N. Suzuki , Takahiro K. Fujiwara , Amine Aladag","doi":"10.1016/j.ceb.2024.102394","DOIUrl":"10.1016/j.ceb.2024.102394","url":null,"abstract":"<div><p>This review examines the dynamic mechanisms underlying cellular signaling, communication, and adhesion via transient, nano-scale, liquid-like molecular assemblies on the plasma membrane (PM). Traditional views posit that stable, solid-like molecular complexes perform these functions. However, advanced imaging reveals that many signaling and scaffolding proteins only briefly reside in these molecular complexes and that micron-scale protein assemblies on the PM, including cell adhesion structures and synapses, are likely made of archipelagoes of nanoliquid protein islands. Borrowing the concept of liquid–liquid phase separation to form micron-scale biocondensates, we propose that these nano-scale oligomers and assemblies are enabled by multiple weak but specific molecular interactions often involving intrinsically disordered regions. The signals from individual nanoliquid signaling complexes would occur as pulses. Single-molecule imaging emerges as a crucial technique for characterizing these transient nanoliquid assemblies on the PM, suggesting a shift toward a model where the fluidity of interactions underpins signal regulation and integration.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102394"},"PeriodicalIF":6.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955067424000735/pdfft?md5=d085efe9ac347419a36769efda9d4dff&pid=1-s2.0-S0955067424000735-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomolecular condensates as drivers of membrane trafficking and remodelling","authors":"Rini Ravindran, Stephen W. Michnick","doi":"10.1016/j.ceb.2024.102393","DOIUrl":"10.1016/j.ceb.2024.102393","url":null,"abstract":"<div><p>Membrane remodelling is essential for the trafficking of macromolecules throughout the cell, a process that regulates various aspects of cellular health and pathology. Recent studies implicate the role of biomolecular condensates in regulating multiple steps of the membrane trafficking pathway including but not limited to the organization of the trafficking machinery, dynamic remodeling of membranes, spatial and functional regulation, and response to cellular signals. The implicated proteins contain key structural elements, most notably prion-like domains within intrinsically disordered regions that are necessary for biomolecular condensate formation at fusion sites in processes like endocytic assembly, autophagy, organelle biosynthesis and synaptic vesicle fusion. Experimental and theoretical advances in the field continue to demonstrate that protein condensates can perform mechanical work, the implications of which can be extrapolated to diverse areas of membrane biology.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102393"},"PeriodicalIF":6.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955067424000723/pdfft?md5=b15433b0d15dc0adceb00f39c63f2c5d&pid=1-s2.0-S0955067424000723-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer E. Jenkins , Mohammad Fazli , Chantell S. Evans
{"title":"Mitochondrial motility modulators coordinate quality control dynamics to promote neuronal health","authors":"Jennifer E. Jenkins , Mohammad Fazli , Chantell S. Evans","doi":"10.1016/j.ceb.2024.102383","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102383","url":null,"abstract":"<div><p>Dysfunction in mitochondrial maintenance and trafficking is commonly correlated with the development of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Thus, biomedical research has been dedicated to understanding how architecturally complex neurons maintain and transport their mitochondria. However, the systems that coordinate mitochondrial QC (quality control) dynamics and trafficking in response to neuronal activity and stress are less understood. Additionally, the degree of integration between the processes of mitochondrial trafficking and QC is unclear. Recent work indicates that mitochondrial motility modulators (i.e., anchors and tethers) help coordinate mitochondrial health by mediating distinct, stress-level-appropriate QC pathways following mitochondrial damage. This review summarizes current evidence supporting the role of two mitochondrial motility modulators, Syntaphilin and Mitofusin 2, in coordinating mitochondrial QC to promote neuronal health. Exploring motility modulators' intricate regulatory molecular landscape may reveal new therapeutic targets for delaying disease progression and enhancing neuronal survival post-insult.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102383"},"PeriodicalIF":6.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955067424000620/pdfft?md5=08fa71fab5e55627d213dd1f2e34fc0a&pid=1-s2.0-S0955067424000620-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disruptions in axonal lysosome transport and its contribution to neurological disease","authors":"Jean-Michel Paumier, Swetha Gowrishankar","doi":"10.1016/j.ceb.2024.102382","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102382","url":null,"abstract":"<div><p>Lysosomes are central to the maintenance of protein and organelle homeostasis in cells. Optimal lysosome function is particularly critical for neurons which are long-lived, non-dividing and highly polarized with specialized compartments such as axons and dendrites with distinct architecture, cargo, and turnover requirements. In recent years, there has been a growing appreciation for the role played by axonal lysosome transport in regulating neuronal development, its maintenance and functioning. Perturbations to optimal axonal lysosome abundance leading to either strong accumulations or dearth of lysosomes are both linked to altered neuronal health and functioning. In this review we highlight how two critical regulators of axonal lysosome transport and abundance, the small GTPase Arl8 and the adaptor protein JIP3, aid in maintaining axonal lysosome homeostasis and how alterations to their levels and activity could contribute to neurodevelopmental and neurodegenerative diseases.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102382"},"PeriodicalIF":6.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anumita Jawahar , Joseph Vermeil , Julien Heuvingh , Olivia du Roure , Matthieu Piel
{"title":"The third dimension of the actin cortex","authors":"Anumita Jawahar , Joseph Vermeil , Julien Heuvingh , Olivia du Roure , Matthieu Piel","doi":"10.1016/j.ceb.2024.102381","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102381","url":null,"abstract":"<div><p>The actin cortex, commonly described as a thin 2-dimensional layer of actin filaments beneath the plasma membrane, is beginning to be recognized as part of a more dynamic and three-dimensional composite material. In this review, we focus on the elements that contribute to the three-dimensional architecture of the actin cortex. We also argue that actin-rich structures such as filopodia and stress fibers can be viewed as specialized integral parts of the 3D actin cortex. This broadens our definition of the cortex, shifting from its simplified characterization as a thin, two-dimensional layer of actin filaments.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102381"},"PeriodicalIF":6.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nucleolar organization and ribosomal DNA stability in response to DNA damage","authors":"Stavroula Boukoura, Dorthe Helena Larsen","doi":"10.1016/j.ceb.2024.102380","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102380","url":null,"abstract":"<div><p>Eukaryotic nuclei are structured into sub-compartments orchestrating various cellular functions. The nucleolus is the largest nuclear organelle: a biomolecular condensate with an architecture composed of immiscible fluids facilitating ribosome biogenesis. The nucleolus forms upon the transcription of the repetitive ribosomal RNA genes (rDNA) that cluster in this compartment. rDNA is intrinsically unstable and prone to rearrangements and copy number variation. Upon DNA damage, a specialized nucleolar-DNA Damage Response (n-DDR) is activated: nucleolar transcription is inhibited, the architecture is rearranged, and rDNA is relocated to the nucleolar periphery. Recent data have highlighted how the composition of nucleoli, its structure, chemical and physical properties, contribute to rDNA stability. In this mini-review we focus on recent data that start to reveal how nucleolar composition and the n-DDR work together to ensure rDNA integrity.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102380"},"PeriodicalIF":7.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141303219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural determinants of intermediate filament mechanics","authors":"Zanetta Kechagia, Matthias Eibauer, Ohad Medalia","doi":"10.1016/j.ceb.2024.102375","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102375","url":null,"abstract":"<div><p>Intermediate filaments (IFs) are integral to the cell cytoskeleton, supporting cellular mechanical stability. Unlike other cytoskeletal components, the detailed structure of assembled IFs has yet to be resolved. This review highlights new insights, linking the complex IF hierarchical assembly to their mechanical properties and impact on cellular functions. While we focus on vimentin IFs, we draw comparisons to keratins, showcasing the distinctive structural and mechanical features that underlie their unique mechanical responses.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102375"},"PeriodicalIF":7.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955067424000541/pdfft?md5=13608a56caaafe2fff0ca297e1e306e8&pid=1-s2.0-S0955067424000541-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Computational tools for cellular scale biophysics","authors":"David B. Stein , Michael J. Shelley","doi":"10.1016/j.ceb.2024.102379","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102379","url":null,"abstract":"<div><p>Mathematical models are indispensable for disentangling the interactions through which biological components work together to generate the forces and flows that position, mix, and distribute proteins, nutrients, and organelles within the cell. To illuminate the ever more specific questions studied at the edge of biological inquiry, such models inevitably become more complex. Solving, simulating, and learning from these more realistic models requires the development of new analytic techniques, numerical methods, and scalable software. In this review, we discuss some recent developments in tools for understanding how large numbers of cytoskeletal filaments, driven by molecular motors and interacting with the cytoplasm and other structures in their environment, generate fluid flows, instabilities, and material deformations which help drive crucial cellular processes.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102379"},"PeriodicalIF":7.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In silico labeling in cell biology: Potential and limitations","authors":"Nitsan Elmalam , Lion Ben Nedava , Assaf Zaritsky","doi":"10.1016/j.ceb.2024.102378","DOIUrl":"https://doi.org/10.1016/j.ceb.2024.102378","url":null,"abstract":"<div><p>In silico labeling is the computational cross-modality image translation where the output modality is a subcellular marker that is not specifically encoded in the input image, for example, in silico localization of organelles from transmitted light images. In principle, in silico labeling has the potential to facilitate rapid live imaging of multiple organelles with reduced photobleaching and phototoxicity, a technology enabling a major leap toward understanding the cell as an integrated complex system. However, five years have passed since feasibility was attained, without any demonstration of using in silico labeling to uncover new biological insight. In here, we discuss the current state of in silico labeling, the limitations preventing it from becoming a practical tool, and how we can overcome these limitations to reach its full potential.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"89 ","pages":"Article 102378"},"PeriodicalIF":7.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterizing intracellular mechanics via optical tweezers-based microrheology","authors":"Bart E. Vos , Till M. Muenker , Timo Betz","doi":"10.1016/j.ceb.2024.102374","DOIUrl":"10.1016/j.ceb.2024.102374","url":null,"abstract":"<div><p>Intracellular organization is a highly regulated homeostatic state maintained to ensure eukaryotic cells’ correct and efficient functioning. Thanks to decades of research, vast knowledge of the proteins involved in intracellular transport and organization has been acquired. However, how these influence and potentially regulate the intracellular mechanical properties of the cell is largely unknown. There is a deep knowledge gap between the understanding of cortical mechanics, which is accessible by a series of experimental tools, and the intracellular situation that has been largely neglected due to the difficulty of performing intracellular mechanics measurements. Recently, tools required for such quantitative and localized analysis of intracellular mechanics have been introduced. Here, we review how these approaches and the resulting viscoelastic models lead the way to a full mechanical description of the cytoplasm, which is instrumental for a quantitative characterization of the intracellular life of cells.</p></div>","PeriodicalId":50608,"journal":{"name":"Current Opinion in Cell Biology","volume":"88 ","pages":"Article 102374"},"PeriodicalIF":7.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S095506742400053X/pdfft?md5=4a178435102fa9d0907e04a321d442f5&pid=1-s2.0-S095506742400053X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}