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Centrosome clustering in cancer cells requires microtubule assembly through a RanGTP-dependent TPX2-KIFC1 interaction. 癌细胞中的中心体聚集需要通过依赖rangtp的TPX2-KIFC1相互作用进行微管组装。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2025-12-30 DOI: 10.1016/j.cub.2025.11.075
Georgina Garrido, Jacopo Scrofani, Ana Arsenijevic, Alvaro Aranguren, Francisco Martínez-Jiménez, Eva Borràs, Eduard Sabidó, Isabelle Vernos

Aneuploidy, chromosomal instability (CIN), and centrosome amplification are hallmarks of aggressive solid tumors. Cancer cells with supernumerary centrosomes ensure bipolar spindle formation by efficiently clustering them at the spindle poles. TPX2 (targeting protein for Xenopus kinesin-like protein 2), a nuclear and microtubule-associated protein, and its partner, the Aurora-A kinase (AURKA), are key mitotic players frequently co-overexpressed in human cancers. TPX2 overexpression ranks first in the CIN70 signature, and both TPX2 and AURKA are part of the CIN4 chromosomal instability signature, with prognostic value in breast cancer patients. Using proximity biotinylation assays (BioID), we identified the mitotic interactome of TPX2 and AURKA. Ten of their high-confidence proximity interactors are highly correlated with TPX2 and AURKA in cancer. We further validate the interaction of TPX2 and AURKA with one of them, KIFC1, a minus-end-directed kinesin-like motor that has a role in centrosome clustering in cancer cells. We show that TPX2 and KIFC1 cooperate to ensure robust acentrosomal microtubule nucleation and organization. Our data show that this mechanism plays a major role in the clustering of supernumerary centrosomes in cancer cells.

非整倍体,染色体不稳定性(CIN)和中心体扩增是侵袭性实体瘤的标志。具有多余中心体的癌细胞通过有效地聚集在纺锤体极点确保双极纺锤体的形成。TPX2 (Xenopus kinase -like protein 2的靶蛋白)是一种核和微管相关蛋白,它的伙伴Aurora-A激酶(AURKA)在人类癌症中经常共同过表达,是有丝分裂的关键参与者。TPX2过表达在CIN70信号中排名第一,TPX2和AURKA都是CIN4染色体不稳定性信号的一部分,在乳腺癌患者中具有预后价值。利用邻近生物素化测定(BioID),我们鉴定了TPX2和AURKA的有丝分裂相互作用组。它们的10个高置信度邻近相互作用因子与癌症中的TPX2和AURKA高度相关。我们进一步验证了TPX2和AURKA与其中之一KIFC1的相互作用,KIFC1是一种负端定向的运动蛋白样马达,在癌细胞的中心体聚集中起作用。我们发现TPX2和KIFC1合作,以确保强大的无丝胞体微管成核和组织。我们的数据表明,这种机制在癌细胞中多余中心体的聚集中起主要作用。
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引用次数: 0
Migrasomes. Migrasomes。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 DOI: 10.1016/j.cub.2025.12.018
Haifeng Jiao, Li Yu

Haifeng Jiao and Li Yu introduce migrasomes, large dynamic vesicular structures that form at the tips or intersections of retraction fibers and function in intercellular communication and cellular homeostasis.

焦海峰和李宇介绍了迁移体,这是一种大型的动态囊泡结构,形成于收缩纤维的尖端或交叉处,在细胞间通讯和细胞内平衡中起作用。
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引用次数: 0
Evolution: Plants vs. animals or sexual conflict? 进化:植物对抗动物还是两性冲突?
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 DOI: 10.1016/j.cub.2025.11.061
David Reznick, Joseph Travis

A recent study suggests that plants evolve reproductive isolation more rapidly than animals. Here, we present an alternative hypothesis: rather than revealing a difference between plants and animals, the study's results reveal how sexual conflict can shape the rate of evolution of reproductive isolation.

最近的一项研究表明,植物的生殖隔离进化比动物更快。在这里,我们提出了另一种假设:该研究的结果揭示了性冲突如何影响生殖隔离的进化速度,而不是揭示植物和动物之间的差异。
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引用次数: 0
Evolution: Neuronal impact on patterning in a regenerating sea anemone. 进化:神经元对再生海葵图案的影响。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 DOI: 10.1016/j.cub.2025.12.006
Thomas W Holstein

A hallmark of animal regeneration is its dependency on a nervous system, although some simple forms, like Hydra, can regenerate without one. A new study has now shown that neurons control positional information in regenerating sea anemone.

动物再生的一个特点是依赖于神经系统,尽管一些简单的形式,如九头蛇,可以在没有神经系统的情况下再生。一项新的研究表明,神经元控制着海葵再生过程中的位置信息。
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引用次数: 0
Genomic signatures of evolution and domestication in the button mushroom Agaricus bisporus. 双孢蘑菇进化与驯化的基因组特征。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2026-01-08 DOI: 10.1016/j.cub.2025.12.008
Zhi-Lin Ling, Guo-Tao Chen, Ming-Zhe Zhang, Qi Wu, Jian-Ping Xu, Bin Cao, Fei Liu, Xin-Bin Ma, Rui-Lin Zhao

The evolutionary and domestication history of mushroom-forming fungi remains poorly understood despite their ecological and economic significance. Here, we present the first large-scale population genomic study of the button mushroom (Agaricus bisporus), the world's most cultivated edible mushroom, integrating resequencing data from 482 global wild and commercial strains. Our analyses reveal a complex evolutionary history shaped by Quaternary glacial cycles. We find that geographic isolation caused by the Quaternary glaciation likely drove A. bisporus divergence around 2 mya centered in North America and Europe, with three distinct varieties, while interglacial expansions facilitated extensive gene flow between populations, promoting mixed origins in current A. bisporus var. bisporus populations. Our analyses demonstrated the white cap trait was the key artificial selective trait for domestication, and we successfully connected this domestication trait and its functional gene and found that cap-color evolution might be associated with the diverse function of AbPPO1, whose allele frequency trajectories supported a similar complex evolution process as the A. bisporus var. bisporus populations. By bridging evolutionary genomics with domestication genetics, our findings underscore the role of historical climate dynamics in shaping the biodiversity of mushroom-forming fungi, illustrate the genetic complexity of the button mushroom domestication, and provide a genomic framework for the utilization and improvement of A. bisporus germplasm resources.

尽管蘑菇形成真菌具有生态和经济意义,但其进化和驯化历史仍然知之甚少。在这里,我们首次对世界上栽培最多的食用菌——双孢蘑菇(Agaricus bisporus)进行了大规模群体基因组研究,整合了来自482个全球野生和商业菌株的重测序数据。我们的分析揭示了一个由第四纪冰川旋回形成的复杂进化史。研究发现,第四纪冰期导致的地理隔离可能推动了以北美和欧洲为中心的2亿年左右双孢蘑菇的分化,形成了三个不同的品种,而间冰期的扩张促进了种群间广泛的基因流动,促进了当前双孢蘑菇变种双孢蘑菇种群的混合起源。结果表明,白帽性状是双孢酵母驯化的关键人工选择性状,并成功地将这一驯化性状与其功能基因联系起来,发现帽色进化可能与AbPPO1的多样化功能有关,其等位基因频率轨迹支持了与双孢酵母变种双孢酵母群体相似的复杂进化过程。通过将进化基因组学与驯化遗传学相结合,我们的研究结果强调了历史气候动力学在塑造蘑菇形成真菌生物多样性中的作用,阐明了纽扣菇驯化的遗传复杂性,并为双孢蘑菇种质资源的利用和改良提供了基因组框架。
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引用次数: 0
De novo meristem development in Marchantia polymorpha requires light and an apical auxin signaling minimum. 多形地香的新生分生组织发育需要光和最低限度的顶端生长素信号。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2025-12-05 DOI: 10.1016/j.cub.2025.11.016
Eva-Sophie Wallner, Natalie Edelbacher, Liam Dolan

Meristems are generative centers from which the bodies of land plants develop. Marchantia polymorpha spores are single cells formed during meiosis that-upon germination-form an early cell mass on which a flat prothallus develops. A single stem cell niche (meristem) develops de novo at the margin of the prothallus to generate the thallus plant body. Here we show that the prothallus forms at the apical pole of the early cell mass and represses the formation of other prothalli in a light- and auxin-dependent manner. Light is required for prothallus development and the formation of an apical auxin signaling minimum, marked by expression of LOW AUXIN RESPONSIVE (MpLAXR). MpLAXR marks the sporeling apex-the site of organogenesis-and predicts the positioning of the future apical stem cell on the prothallus. Ablation of the dominant prothallus induces the development of a suppressed prothallus in a process comparable to apical dominance. A similar molecular program operates during plant regeneration from a single differentiated thallus cell, which regains stemness (pluripotency) upon surgical isolation from its tissue context, and the isolated cell divides, forming an early cell mass with an MpLAXR-expressing apex where a flat prothallus with a single meristem forms. We conclude that a light-dependent, apical auxin signaling minimum is required for the formation of the prothallus and the de novo development of the first meristem in Marchantia polymorpha.

分生组织是陆地植物体发育的生殖中心。多形地香孢子是在减数分裂过程中形成的单细胞,在萌发后形成一个早期的细胞团,在这个细胞团上形成扁平的原体。单个干细胞生态位(分生组织)在原体边缘重新发育,形成原体植物体。在这里,我们发现原体形成于早期细胞团的顶极,并以光和生长素依赖的方式抑制其他原体的形成。光是原体发育和顶端生长素信号最小值的形成所必需的,其标志是低生长素响应蛋白(LOW auxin RESPONSIVE, MpLAXR)的表达。MpLAXR标记了裂尖——器官发生的位置——并预测了未来顶端干细胞在原体上的位置。优势原体的消融诱导抑制原体的发育,其过程与顶端优势相当。类似的分子程序在单个分化的体块细胞的植物再生过程中起作用,该体块在手术分离后从其组织环境中恢复干性(多能性),并且分离的细胞分裂,形成具有表达mplaxr的顶端的早期细胞团,其中形成具有单个分生组织的扁平原体。我们得出结论,在多形地豆原体的形成和第一个分生组织的新生发育中,需要一个光依赖性的顶端生长素信号最低限度。
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引用次数: 0
Inhibition of receptor-mediated endocytosis by the amphiphysin SH3 domain. 两性蛋白SH3结构域对受体介导的内吞作用的抑制。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2025-12-19 DOI: 10.1016/j.cub.2025.12.020
Patrick Wigge, Yvonne Vallis, Harvey T McMahon
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引用次数: 0
FERONIA kinase and PP2A antagonistically regulate salt tolerance in Arabidopsis. FERONIA激酶和PP2A拮抗拟南芥耐盐性。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2025-12-19 DOI: 10.1016/j.cub.2025.11.064
Jianwei Liu, Mingtao Wang, Xin Liu, Xiaoxiao Wang, Zhihui Li, Jinyan Luo, Wenhui Lin, Chunzhao Zhao

Leucine-rich repeat extensin (LRX) 3/4/5 and FERONIA (FER) jointly regulate plant salt tolerance, but the mechanisms by which LRX3/4/5 modulate FER activity in response to salt stress remain largely unclear. Here, we found that lrx345 mutations reduce FER kinase activity, which explains the phenotypic similarity between lrx345 and fer-4. Immunoprecipitation-mass spectrometry (IP-MS) analysis reveals a physical interaction between FER and protein phosphatase 2A (PP2A), with PP2A directly dephosphorylating FER. Disruption of PP2A restores FER kinase activity and salt hypersensitivity in the lrx345 mutant, establishing PP2A as a key negative regulator of FER kinase activity. Conversely, FER inhibits PP2A phosphatase activity through phosphorylation, forming a dynamic feedback loop. Further mechanistic studies show that FER and PP2A coordinately regulate plant salt tolerance by controlling auxin transport via the modulation of PIN3 phosphorylation. Collectively, our work unveils an antagonistic kinase-phosphatase pair that fine-tunes phosphorylation-dependent signaling to optimize plant adaptation to salt stress.

富亮氨酸重复延伸蛋白(Leucine-rich repeat extensin, LRX) 3/4/5和FERONIA (FERONIA, FER)共同调控植物耐盐性,但LRX3/4/5在盐胁迫下调控FER活性的机制尚不清楚。在这里,我们发现lrx345突变降低了FER激酶活性,这解释了lrx345与FER -4之间的表型相似性。免疫沉淀-质谱(IP-MS)分析揭示了FER与蛋白磷酸酶2A (PP2A)之间的物理相互作用,PP2A直接使FER去磷酸化。在lrx345突变体中,PP2A的破坏恢复了FER激酶活性和盐敏感性,确立了PP2A是FER激酶活性的关键负调控因子。相反,FER通过磷酸化抑制PP2A磷酸酶活性,形成动态反馈回路。进一步的机制研究表明,FER和PP2A通过调节PIN3磷酸化调控生长素运输,从而协同调节植物耐盐性。总的来说,我们的工作揭示了一种拮抗激酶-磷酸酶对,它可以微调磷酸化依赖的信号,以优化植物对盐胁迫的适应。
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引用次数: 0
Decoupling of visual feature selectivity in the retinocollicular pathway. 视网膜视丘通路中视觉特征选择性的解耦。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 Epub Date: 2025-12-16 DOI: 10.1016/j.cub.2025.11.050
Ole S Schwartz, Akihiro Matsumoto, Haruka Yamamoto, Keisuke Yonehara

The retina is composed of discrete functional cell types that are also characterized by distinct morphology and gene expression. It remains, however, unclear whether similar discrete functional cell types exist in the visual regions downstream of the retina. Here, we used two-photon calcium imaging to investigate the response-space structure in the retina and in the superficial layers of the mouse superior colliculus (SC), a major retinorecipient area. We found that although retinal ganglion cells showed a clear dependence between responses to luminance and motion, responses to the two stimuli exhibited weaker couplings in collicular neurons. Because of this decoupling, functional clustering based on responses to both luminance and motion had significantly reduced separability compared with clustering based on responses to either. Our work suggests that the SC is not simply a relay station for retinal inputs but rather generates novel feature selectivity that diversifies cellular responses, perhaps through nonlinear neural processes involving the decoupling and recoupling of retinal ganglion cells' feature selectivity.

视网膜由离散的功能细胞类型组成,这些细胞类型也以不同的形态和基因表达为特征。然而,目前尚不清楚在视网膜下游的视觉区域是否存在类似的离散功能细胞类型。在这里,我们使用双光子钙成像来研究视网膜和小鼠上丘(SC)浅层的反应空间结构,上丘是一个主要的视网膜受体区域。我们发现,尽管视网膜神经节细胞对亮度和运动的反应表现出明显的依赖性,但对两种刺激的反应在丘脑神经元中表现出较弱的耦合。由于这种解耦,基于亮度和运动响应的功能聚类与基于两者响应的聚类相比,显著降低了可分离性。我们的工作表明,SC不仅仅是视网膜输入的中继站,而是产生新的特征选择性,使细胞反应多样化,这可能是通过涉及视网膜神经节细胞特征选择性的解耦和再耦合的非线性神经过程。
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引用次数: 0
Flexible use of a multi-purpose tool by a cow. 牛灵活地使用一种多用途工具。
IF 7.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-19 DOI: 10.1016/j.cub.2025.11.059
Antonio J Osuna-Mascaró, Alice M I Auersperg

Imagine the tools a cow would make. This idea, humorously illustrated in Gary Larson's Far Side cartoon, captures a widespread assumption: cows are neither problem-solvers nor tool users. In science, as in culture, livestock species are often cognitively underestimated, reinforced by their utilitarian role and persistent mind-denial biases associated with meat consumption1. Despite over 10,000 years of domestication, research on cattle cognition remains scarce and confined to applied contexts such as productivity and welfare2. Tool use, while rarely observed, offers a stringent test of cognitive flexibility. Defined as the manipulation of an external object to achieve a goal via a mechanical interface3, tooling ranges from species-typical routines to innovative, problem-specific acts4,5. We report here our experimental demonstration of flexible egocentric tooling in a pet cow (Bos taurus), Veronika, who uses a deck brush to self-scratch. Across randomized trials, she preferred the bristled end but switched to the stick end when targeting softer lower-body areas. This adaptive deployment of tool features reveals multi-purpose tool use not previously reported in non-primate mammals. Our findings broaden the taxonomic scope of flexible tool use and invite a reassessment of livestock cognition. VIDEO ABSTRACT.

想象一下一头牛会制造出什么样的工具。加里·拉尔森(Gary Larson)的《远方》(Far Side)漫画幽默地阐释了这一观点,它抓住了一个普遍存在的假设:奶牛既不会解决问题,也不会使用工具。在科学上,就像在文化上一样,牲畜在认知上经常被低估,它们的功利主义作用和与肉类消费有关的持续的思维否认偏见强化了这一点。尽管牛已经被驯化了1万多年,但对牛认知的研究仍然很少,而且仅限于生产力和福利等应用领域。工具的使用,虽然很少被观察到,但提供了对认知灵活性的严格测试。工装被定义为通过机械接口对外部对象进行操作以实现目标,工装的范围从典型的常规操作到创新的、特定问题的行为4,5。我们在这里报告我们的实验演示灵活的自我中心的工具在宠物牛(Bos金牛座),维罗妮卡,谁使用甲板刷自刮。在随机试验中,她更喜欢鬃毛末端,但在针对较柔软的下半身区域时,她会切换到棍子末端。这种工具特征的自适应部署揭示了非灵长类哺乳动物先前未报道的多用途工具使用。我们的发现拓宽了灵活工具使用的分类范围,并引发了对牲畜认知的重新评估。视频摘要。
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引用次数: 0
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