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License to drive: Receptor-mediated ER exit of proteins and lipids 驾驶执照：受体介导的蛋白质和脂质内质网出口。
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-20 DOI: 10.1016/j.ceb.2025.102501
Xiao Wang , Tiantian Li , Yusong Guo , Xiao-Wei Chen
The secretory pathway, which begins at the endoplasmic reticulum (ER) through the COPII complex, is responsible for transporting proteins and lipid carriers to various destined cellular compartments or extracellular space. The fundamental mechanism by which the COPII operates is evolutionarily conserved. Nevertheless, the vast diversity of mammalian cargos poses significant challenges to the secretory pathway, especially considering the intricate physiology in vivo. Particularly, certain physiologically essential cargos, including procollagen and lipoproteins, appear to be oversized for these canonical carriers, implying the need for additional sophisticated regulation at the onset step so-called ER exit. Emerging evidence highlights the critical role of cargo receptors in selective sorting for ER export, illuminating the complex biology of the trafficking dynamics, which holds broad implications for human health and diseases.
分泌途径始于内质网（ER），通过COPII复合物，负责将蛋白质和脂质载体运送到各种指定的细胞室或细胞外空间。COPII运作的基本机制是进化保守的。然而，哺乳动物物质的巨大多样性对分泌途径提出了重大挑战，特别是考虑到复杂的体内生理。特别是，某些生理上必需的货物，包括前胶原蛋白和脂蛋白，对于这些典型的载体来说似乎过大，这意味着需要在所谓的内质网退出的起始阶段进行额外的复杂调节。新出现的证据突出了货物受体在ER出口的选择性分类中的关键作用，阐明了贩运动态的复杂生物学，这对人类健康和疾病具有广泛的影响。
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引用次数: 0
Organizing principles underlying COPII-mediated transport copii介导转运的组织原则
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-10 DOI: 10.1016/j.ceb.2025.102492
Julia R. Flood, Caitlin A. Mendina, Anjon Audhya
The early secretory pathway governs the transport of thousands of secreted and transmembrane proteins and lipids from the endoplasmic reticulum (ER) to juxtaposed ER-Golgi Intermediate Compartments (ERGIC). This process is largely directed by Coat Protein complex II (COPII), which accumulates on distinct, ribosome-free ER subdomains (transitional ER) to generate highly curved transport intermediates of various sizes and shapes. The rate of secretory flux from the ER can vary significantly, depending on cell type, environmental cues, and other factors, but the mechanisms that regulate COPII-mediated trafficking have been slow to emerge. Here, we focus on recent progress that has contributed to our understanding of how the early secretory pathway is structured to facilitate the export of cargoes from the ER into a chasm approximately 300–500-nm in size, prior to fusion with ERGIC membranes without the aid of cytoskeletal elements to guide their journey.
早期分泌途径控制着数千种分泌蛋白、跨膜蛋白和脂质从内质网（ER）向并列的ER-高尔基中间区室（ERGIC）的运输。这一过程主要由衣壳蛋白复合物 II（COPII）引导，COPII 在不同的、无核糖体的 ER 亚域（过渡 ER）上聚集，生成各种尺寸和形状的高度弯曲的运输中间体。ER分泌通量的速率会因细胞类型、环境线索和其他因素的不同而发生显著变化，但调控COPII介导的转运的机制却迟迟没有出现。在此，我们将重点介绍最近的研究进展，这些进展有助于我们了解早期分泌途径的结构是如何促进货物从ER输出到约300-500纳米大小的鸿沟中，然后与ERGIC膜融合，而无需借助细胞骨架元件来引导货物的旅程。
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引用次数: 0
High-dimensional signalling analysis of organoids 类器官的高维信号分析
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-09 DOI: 10.1016/j.ceb.2025.102488
Aurélie Dobric, Christopher J. Tape
Cellular phenotypes are regulated by dynamic signalling processes that involve proteins, post-translational modifications, epigenetic events, and transcriptional responses. Functional perturbation studies are required to understand cell signalling mechanisms and organoids have recently emerged as scalable biomimetic models amenable to large-scale perturbation. Here, we review the recent advances in high-dimensional analysis of cell signalling in organoids. Single-cell technologies provide cell-type specific analysis of multiple biochemical modalities, enabling a deeper understanding of the signalling mechanisms driving cell-fate dynamics. Emerging multimodal techniques are further revealing coordination between signalling layers and are poised to increase our mechanistic understanding of cell signalling.
细胞表型受动态信号过程调控，其中涉及蛋白质、翻译后修饰、表观遗传事件和转录反应。要了解细胞信号机制，需要进行功能扰动研究，而最近出现的有机体是一种可扩展的生物仿生模型，适合进行大规模扰动。在此，我们回顾了有机体细胞信号高维分析的最新进展。单细胞技术可对多种生化模式进行细胞类型特异性分析，从而加深对驱动细胞命运动态的信号机制的理解。新兴的多模态技术正在进一步揭示信号层之间的协调，并有望加深我们对细胞信号机制的理解。
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引用次数: 0
Multifaceted regulation of asymmetric cell division by the actin cytoskeleton 肌动蛋白细胞骨架对不对称细胞分裂的多方面调控
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-07 DOI: 10.1016/j.ceb.2025.102491
Peishan Yi , Guangshuo Ou , Wei Li
Asymmetric cell division (ACD) is essential for generating cell diversity in multicellular eukaryotes, yet the underlying mechanisms remain largely unresolved. Well-established models of ACD, such as microtubule-based spindle displacement in Caenorhabditis elegans embryos and preprophase band assembly in plants provide valuable insights but fail to fully explain asymmetry establishment in others. In this article, we discuss how actin-dependent mechanisms govern ACD in model systems, highlighting emerging commonalities and differences. Given its broad impact, the actin cytoskeleton may play a more significant role in ACD than currently recognized, serving as a fundamental component during organismal development across kingdoms.
在多细胞真核生物中，不对称细胞分裂（ACD）是产生细胞多样性的必要条件，但其潜在机制在很大程度上仍未得到解决。成熟的ACD模型，如秀丽隐杆线虫胚胎中基于微管的纺锤体位移和植物的前期带组装，提供了有价值的见解，但不能完全解释其他不对称的建立。在本文中，我们讨论了作用蛋白依赖机制如何在模型系统中控制ACD，突出了新出现的共性和差异。鉴于其广泛的影响，肌动蛋白细胞骨架可能在ACD中发挥比目前认识到的更重要的作用，作为跨王国生物体发育的基本组成部分。
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引用次数: 0
Aneuploidy as a cancer vulnerability 作为癌症易发因素的非整倍体
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-06 DOI: 10.1016/j.ceb.2025.102490
Jinghui Cao , Cai Liang , Hongtao Yu
Aneuploidy is prevalent in cancer and has complicated roles in tumorigenesis. Paradoxically, artificially engineered aneuploidy in normal cells reduces cellular fitness by inducing proteotoxic and genotoxic stresses. A better molecular understanding of the multifaceted roles of aneuploidy in cancer evolution offers promising avenues for future cancer therapies. Here, we discuss the patterns and consequences of aneuploidy in human cancer. We highlight recent efforts to explore aneuploidy as a cancer vulnerability and new interventions that exploit this vulnerability for cancer treatment.
非整倍体在癌症中普遍存在，在肿瘤发生中具有复杂的作用。矛盾的是，正常细胞中的人工工程非整倍体通过诱导蛋白质毒性和基因毒性应激降低了细胞适应性。对非整倍体在癌症进化中的多方面作用的更好的分子理解为未来的癌症治疗提供了有希望的途径。在这里，我们讨论非整倍体在人类癌症的模式和后果。我们强调了最近探索非整倍体作为癌症易感性和利用这种易感性进行癌症治疗的新干预措施的努力。
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引用次数: 0
Editorial overview: Cell dynamics across biological length scales 编辑概述：跨越生物长度尺度的细胞动力学
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-03 DOI: 10.1016/j.ceb.2025.102489
Matthew L. Kutys, Robert Grosse
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引用次数: 0
Outside Back Cover 外封底
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-03 DOI: 10.1016/S0955-0674(25)00038-9
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引用次数: 0
The functional organisation of the centromere and kinetochore during meiosis 减数分裂过程中着丝粒和着丝粒的功能组织
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-02-26 DOI: 10.1016/j.ceb.2025.102486
Lori B. Koch, Adele L. Marston
Meiosis generates gametes through a specialised cell cycle that reduces the genome by half. Homologous chromosomes are segregated in meiosis I and sister chromatids are segregated in meiosis II. Centromeres and kinetochores play central roles in instructing this specialised chromosome segregation pattern. Accordingly, kinetochores acquire meiosis-specific modifications. Here we contextualise recent highlights in our understanding of how centromeres and kinetochores direct the sorting of chromosomes into gametes via meiosis.
减数分裂通过一个特殊的细胞周期产生配子，这个周期将基因组减少一半。同源染色体在减数分裂I中分离，姐妹染色单体在减数分裂II中分离。着丝粒和着丝点在指导这种特殊的染色体分离模式中起着核心作用。因此，着丝点获得减数分裂特异性修饰。在这里，我们对着丝粒和着丝点如何通过减数分裂指导染色体分选进入配子的理解中的最新亮点进行了背景分析。
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引用次数: 0
Navigating confinement: Mechanotransduction and metabolic adaptation 导航限制：机械转导和代谢适应
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-02-24 DOI: 10.1016/j.ceb.2025.102487
Alice Amitrano , Debanik Choudhury , Konstantinos Konstantopoulos
Cell migration through confined spaces is a critical process influenced by the complex three-dimensional (3D) architecture of the local microenvironment and the surrounding extracellular matrix (ECM). Cells in vivo experience diverse fluidic signals, such as extracellular fluid viscosity, hydraulic resistance, and shear forces, as well as solid cues, like ECM stiffness and viscoelasticity. These fluidic and solid stressors activate mechanotransduction processes and regulate cell migration. They also drive metabolic reprogramming, dynamically altering glycolysis and oxidative phosphorylation to meet the cell's energy demands in different microenvironments. This review discusses recent advances on the mechanisms of cell migration in confinement and how confinement-induced cellular behavior leads to metabolic reprogramming.
细胞在密闭空间内的迁移是一个受局部微环境的复杂三维（3D）结构和周围细胞外基质（ECM）影响的关键过程。细胞在体内经历不同的流体信号，如细胞外流体粘度、水力阻力和剪切力，以及固体信号，如ECM刚度和粘弹性。这些流体和固体压力源激活机械转导过程并调节细胞迁移。它们还驱动代谢重编程，动态改变糖酵解和氧化磷酸化，以满足不同微环境下细胞的能量需求。本文综述了禁闭中细胞迁移机制的最新进展，以及禁闭诱导的细胞行为如何导致代谢重编程。
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引用次数: 0
Centrosome biogenesis and maintenance in homeostasis and disease 体内平衡和疾病中的中心体生物发生和维持
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-02-24 DOI: 10.1016/j.ceb.2025.102485
Camila Fernandes-Mariano , Joana N. Bugalhão , Diana Santos , Mónica Bettencourt-Dias
Recent technological advances in proteomics and microscopy techniques, such as cryo-electron microscopy (cryoEM) and expansion microscopy (ExM), have enhanced our understanding of centrosome structure, biogenesis, and regulation. Here we discuss new insights into centrosome structure, highlight new regulatory mechanisms in centrosome biogenesis, and explore emerging concepts in centrosome maintenance and plasticity across different contexts. Furthermore, we review how centrosome biogenesis and homeostasis are dysregulated in various pathological conditions. We finalise by outlining outstanding questions in the field, how the mechanisms discussed are regulated across multiple contexts, the balance between centriole stability and plasticity, and the therapeutic potential of targeting centrosome dysfunction in disease.
蛋白质组学和显微技术的最新技术进步，如低温电子显微镜（cryoEM）和扩增显微镜（ExM），增强了我们对中心体结构、生物发生和调控的理解。在这里，我们讨论了中心体结构的新见解，重点介绍了中心体生物发生的新调控机制，并探讨了中心体维持和可塑性在不同背景下的新概念。此外，我们回顾了中心体生物发生和体内平衡在各种病理条件下是如何失调的。最后，我们概述了该领域的突出问题，所讨论的机制如何在多种情况下受到调节，中心粒稳定性和可塑性之间的平衡，以及针对疾病中中心体功能障碍的治疗潜力。
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