Molecules and Cells最新文献

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N-Terminal deleted isoforms of E3 ligase RNF220 are ubiquitously expressed and required for mouse muscle differentiation E3连接酶RNF220 n端缺失异构体普遍表达，是小鼠肌肉分化所必需的。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 DOI: 10.1016/j.mocell.2025.100250

SeokGyeong Choi , Sojung Ha , Donald J. Wolfgeher , Jee Won Kim , Young-Hyun Go , Hyuk-Jin Cha , Gyu-Un Bae , Stephen J. Kron , Woo-Young Kim

Four isoform peptides of the novel E3 ligase ring finger protein 220 (RNF220) have been identified in humans. However, all of the previous studies have predominantly focused on isoform 1 (the full-length form), which consists of 566 amino acids. Here, we show that a shorter isoform, which is 308 amino acids lacking most of the N-terminus (human isoform 4; mouse isoform 3; ΔN-RNF220), is the predominant and ubiquitously expressed variant that warrants functional investigation. Both isoform 1 and ΔN-RNF220 are expressed in the brain; however, ΔN-RNF220 is the major isoform expressed in all other tissues in mice. Consistently, H3K4me3 ChIP-seq data from ENCODE reveal that the transcription start site for ΔN-RNF220 demonstrates broader and stronger activity across human tissues than that of isoform 1. ΔN-RNF220 produces 2 peptides (4a and 4b) through alternative translation initiation, with isoform 4b displaying distinct subcellular localization, subnuclear structures and interaction with a nuclear protein WDR5. Notably, during embryonic stem cell differentiation into neural stem cells, isoform 1 expression increases, whereas ΔN-RNF220 expression decreases. In murine myoblasts, ΔN-RNF220 is the sole expressed isoform and is required for MyoD and myogenin expression, as well as for muscle differentiation. Our findings highlight ΔN-RNF220 as the ubiquitously and highly expressed variant, likely playing a fundamental role across tissues while exhibiting functional differences from isoform 1. These results emphasize the critical importance of ΔN-RNF220 in future studies investigating the biological functions of RNF220.

新型E3连接酶RNF220的四种异构体肽已在人类中被鉴定出来。然而，所有先前的研究主要集中在异构体1（全长形式）上，它由566个氨基酸（aa）组成。在这里，我们展示了一个更短的异构体，它是308 aa，缺乏大部分的n端(人类异构体4；小鼠亚型3；ΔN-RNF220)，是主要的和普遍表达的变体，值得功能性研究。同种异构体1和ΔN-RNF220都在大脑中表达；然而，ΔN-RNF220是小鼠所有其他组织中表达的主要亚型。同样，ENCODE的H3K4me3 ChIP-seq数据显示，ΔN-RNF220的转录起始位点在人体组织中的活性比同种异构体1更广泛、更强。ΔN-RNF220通过替代翻译起始产生两种肽（4a和4b），其中4b异构体显示不同的亚细胞定位、亚核结构并与核蛋白WDR5相互作用。值得注意的是，在胚胎干细胞向神经干细胞分化的过程中，isoform 1表达增加，而ΔN-RNF220表达减少。在小鼠成肌细胞中，ΔN-RNF220是唯一表达的同种异构体，是MyoD和肌原素表达以及肌肉分化所必需的。我们的研究结果强调ΔN-RNF220是普遍存在的高表达变体，可能在组织中发挥基本作用，同时表现出与异构体1的功能差异。这些结果强调了ΔN-RNF220在未来研究RNF220生物学功能的关键重要性。

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引用次数: 0

Brief guide to Caenorhabditis elegans imaging and quantification 秀丽隐杆线虫成像与定量简介。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-29 DOI: 10.1016/j.mocell.2025.100249

Hyemin Min, Gyutae Park, Seung-Jae V. Lee

Caenorhabditis elegans is a powerful model organism for fluorescence imaging to study gene regulation and cellular biomarkers. This concise MiniResource introduces essential imaging techniques for live and fixed C. elegans, sample preparations, microscopy, and common applications. We also outline basic image analysis workflows using open-source software. This guideline serves as a practical resource for researchers who seek implementing fluorescence imaging with C. elegans.

秀丽隐杆线虫是荧光成像研究基因调控和细胞生物标志物的有力模式生物。这个简洁的MiniResource介绍了活体和固定秀丽隐杆线虫，样品制备，显微镜和常见应用的基本成像技术。我们还概述了使用开源软件的基本图像分析工作流程。本指南作为一个实用的资源，为研究人员寻求实现荧光成像与秀丽隐杆线虫。

引用次数: 0

Advancing precision diagnosis in autism: Insights from large-scale genomic studies 推进自闭症的精确诊断：来自大规模基因组研究的见解。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-26 DOI: 10.1016/j.mocell.2025.100248

Soo-Whee Kim , Joon-Yong An

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex genetic basis. Large-scale whole-exome sequencing and whole-genome sequencing studies, with increasing sample sizes and improved ancestral diversity, have significantly advanced the discovery of ASD-associated genes. In addition to identifying coding variants, whole-genome sequencing has facilitated the detection of risk noncoding variants in regulatory elements such as enhancers, promoters, and untranslated regions, prompting experimental validation of their functional impact on neurodevelopment. A deeper understanding of ASD genetic liability has revealed the interplay between rare and common variants. Moreover, genetic liability varies by sex and phenotype profile, underscoring the complexity of ASD’s genetic architecture. While the clinical application of these genomic insights remains in early stages, progress has been made in gene-based therapeutic development, the interpretation of noncoding risk variants, and the use of polygenic score for risk stratification. In this review, we summarize key findings from large-scale genomic studies, explore the role of coding and noncoding variants in ASD, and discuss emerging opportunities for translating these discoveries into clinical practice.

自闭症谱系障碍（ASD）是一种具有复杂遗传基础的神经发育疾病。大规模全外显子组测序（WES）和全基因组测序（WGS）研究，随着样本量的增加和祖先多样性的提高，显著推进了asd相关基因的发现。除了识别编码变异外，WGS还有助于检测调节元件（如增强子、启动子和非翻译区域）中的风险非编码变异，从而促进实验验证其对神经发育的功能影响。对自闭症谱系障碍遗传倾向的深入了解揭示了罕见和常见变异之间的相互作用。此外，遗传倾向因性别和表型而异，强调了ASD遗传结构的复杂性。虽然这些基因组学见解的临床应用仍处于早期阶段，但在基于基因的治疗开发、非编码风险变异的解释以及使用多基因评分进行风险分层方面取得了进展。在这篇综述中，我们总结了大规模基因组研究的主要发现，探讨了编码和非编码变异在ASD中的作用，并讨论了将这些发现转化为临床实践的新机会。

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引用次数: 0

Optogenetics to biomolecular phase separation in neurodegenerative diseases 神经退行性疾病的光遗传学与生物分子相分离。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-22 DOI: 10.1016/j.mocell.2025.100247

Kyung Hwan Park, Kyung Won Kim

Neurodegenerative diseases involve toxic protein aggregation. Recent evidence suggests that biomolecular phase separation, a process in which proteins and nucleic acids form dynamic, liquid-like condensates, plays a key role in this aggregation. Optogenetics, originally developed to control neuronal activity with light, has emerged as a powerful tool to investigate phase separation in living systems. This is achieved by fusing disease-associated proteins to light-sensitive oligomerization domains, enabling researchers to induce or reverse condensate formation with precise spatial and temporal control. This review highlights how optogenetic systems such as OptoDroplet are being used to dissect the mechanisms of neurodegenerative disease. We examine how these tools have been applied in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s, and Huntington’s disease. These studies implicate small oligomeric aggregates as key drivers of toxicity and highlight new opportunities for therapeutic screening. Finally, we discuss advances in light-controlled dissolution of condensates and future directions for applying optogenetics to combat neurodegeneration. By enabling precise, dynamic control of protein phase behavior in living systems, optogenetic approaches provide a powerful framework for elucidating disease mechanisms and informing the development of targeted therapies.

神经退行性疾病涉及毒性蛋白聚集。最近的证据表明，生物分子相分离，蛋白质和核酸形成动态的液体状凝聚体的过程，在这种聚集中起着关键作用。光遗传学最初是为了用光控制神经元活动而发展起来的，现在已经成为研究生命系统中相分离的有力工具。这是通过将疾病相关蛋白融合到光敏寡聚化结构域来实现的，使研究人员能够通过精确的空间和时间控制诱导或逆转冷凝物的形成。本文综述了光遗传系统（如OptoDroplet）如何被用于分析神经退行性疾病的机制。我们研究了这些工具如何应用于神经退行性疾病的模型，如肌萎缩性侧索硬化症、阿尔茨海默病、帕金森病和亨廷顿病。这些研究表明，小的寡聚物聚集体是毒性的关键驱动因素，并强调了治疗筛选的新机会。最后，我们讨论了光遗传学在光控制凝聚物溶解方面的研究进展，以及应用光遗传学治疗神经退行性疾病的未来方向。通过对生命系统中蛋白质相行为的精确、动态控制，光遗传学方法为阐明疾病机制和为靶向治疗的发展提供了强有力的框架。

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引用次数: 0

Dietary salt induces taste desensitization via receptor internalization in Drosophila in a sexually dimorphic manner 饮食盐诱导味觉脱敏通过受体内化在果蝇在两性二态的方式。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-18 DOI: 10.1016/j.mocell.2025.100242

Linni Jin , Chul Hoon Kim , Jeong Taeg Seo , Seok Jun Moon

Sodium homeostasis, which is critical for survival, includes mechanisms for regulating salt intake that integrate central neural pathways with the peripheral taste system. Although the central homeostatic mechanisms of salt appetite are well-studied, the mechanisms by which dietary salt modulates peripheral taste responses remain unclear. We found increased dietary salt reduces salt preference in Drosophila by desensitizing sweet gustatory receptor neurons independent of internal sodium levels. We observed a reversible suppression of salt-evoked neural responses following salt exposure accomplished via clathrin-mediated endocytosis in males and both clathrin- and C-terminal binding protein-dependent endocytosis in females. We also found reversing gustatory receptor neuron sexual identity switched the desensitization pattern, indicating cell-autonomous control of this sexual dimorphism. Moreover, C-terminal binding protein-mediated macropinocytosis in females also dampened sweet taste responses, revealing a sex- and modality-specific mechanism underlying sensory adaptation. These findings reveal dietary experience can affect feeding behavior by reprograming peripheral taste responses, clarifying the plasticity of nutrient sensing.

钠稳态对生存至关重要，包括调节盐摄入量的机制，该机制整合了中枢神经通路和外周味觉系统。虽然盐食欲的中心稳态机制已经得到了很好的研究，但饮食盐调节周围味觉反应的机制仍然不清楚。我们发现增加的饮食盐通过使独立于体内钠水平的甜味味觉受体神经元（grn）脱敏，降低了果蝇对盐的偏好。我们观察到盐暴露后盐诱发的神经反应的可逆抑制，通过网格蛋白介导的雄性内吞作用和网格蛋白和ctbp依赖的雌性内吞作用完成。我们还发现，逆转GRN性别身份改变了脱敏模式，表明细胞自主控制这种性别二态性。此外，ctbp介导的雌性巨噬细胞增多症也会抑制甜味反应，揭示了一种基于性别和模式的感觉适应机制。这些发现表明，饮食体验可以通过重编程周围味觉反应来影响摄食行为，阐明营养感知的可塑性。

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引用次数: 0

Analysis of mitochondrial membrane potential, ROS, and calcium 线粒体膜电位、活性氧和钙的分析。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-16 DOI: 10.1016/j.mocell.2025.100238

Hye-Kyung Park, Byoung Heon Kang

Mitochondria play a central role in cellular energy metabolism and signaling, and their dysfunction is associated with a wide range of diseases. Therefore, assessing mitochondrial function is essential for understanding their role in various cellular processes and disease progression. Here, we describe the principles and methodologies for analyzing mitochondrial membrane potential, reactive oxygen species, and calcium levels using the fluorescent probes tetramethylrhodamine methyl ester, MitoSOX, and Rhod-2AM, respectively. This work provides a practical guide for researchers investigating mitochondrial function under physiological and pathological conditions.

线粒体在细胞能量代谢和信号传导中起着核心作用，其功能障碍与多种疾病有关。因此，评估线粒体功能对于了解它们在各种细胞过程和疾病进展中的作用至关重要。在这里，我们描述了使用荧光探针TMRM、MitoSOX和Rhod-2AM分别分析线粒体膜电位、活性氧和钙水平的原理和方法。这项工作为研究人员在生理和病理条件下研究线粒体功能提供了实用指南。

引用次数: 0

RNA-associated nuclear condensates: Where the nucleus keeps its RNAs in check rna相关核凝聚物：细胞核控制rna的地方。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-15 DOI: 10.1016/j.mocell.2025.100240

Doyeong Ku , Yewon Yang , Yoosik Kim

Noncoding RNAs (ncRNAs) are emerging regulators of cellular processes and stress response by controlling chromatin architecture and gene expression. Recent studies have revealed that these ncRNAs functions are closely associated with nuclear condensates, membrane-less compartments formed by liquid-liquid phase separation (LLPS) that provide a specialized subnuclear environment for genome organization as well as transcriptional and post-transcriptional regulation. Disruption of RNA-mediated nuclear condensates is increasingly linked to human diseases, including neurodegenerative disease and cancer, emphasizing their essential role in maintaining cellular homeostasis. Advances in high-resolution microscopy and high-throughput sequencing have elucidated subcompartmental structures and genetic components of nuclear condensates by identifying associated RNA molecules and providing the details of RNA-protein interactions at a single-nucleotide resolution. We now understand that ncRNAs act as scaffolds that recruit RNA-binding proteins with intrinsically disordered domains to trigger the nucleation event for LLPS, resulting in the formation of nuclear condensates. In this review, we summarize how RNAs and RNA-binding proteins contribute to RNA-mediated nuclear condensate formation via LLPS and support their regulatory functions.

非编码rna （ncRNAs）是通过控制染色质结构和基因表达来调控细胞过程和应激反应的新兴调控因子。最近的研究表明，这些ncRNAs的功能与rna介导的核凝聚体密切相关，核凝聚体是由液-液相分离（LLPS）形成的无膜隔间，为基因组组织以及转录和转录后调控提供了一个专门的亚核环境。rna介导的核凝聚物的破坏越来越多地与人类疾病，包括神经退行性疾病和癌症联系在一起，强调了它们在维持细胞稳态中的重要作用。高分辨率显微镜和高通量测序技术的进步，通过鉴定相关的RNA分子，并在单核苷酸分辨率上提供RNA-蛋白相互作用的细节，阐明了核凝聚物的亚室结构和遗传成分。我们现在了解到，ncRNAs作为支架，招募具有内在无序结构域的rna结合蛋白（rbp）来触发LLPS的成核事件，导致核凝聚物的形成。在这篇综述中，我们总结了rna和rbp如何通过LLPS参与rna介导的核凝析物形成并支持其调节功能。

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引用次数: 0

Pattern recognition receptors and inflammasome: Now and beyond 模式识别受体和炎性体：现在和未来。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-15 DOI: 10.1016/j.mocell.2025.100239

SuHyeon Oh , Young Ki Choi , SangJoon Lee

Pattern recognition receptors (PRRs) are fundamental to the innate immune system, functioning to detect and eliminate invading pathogens by inhibiting their replication and limiting host tissue damage. Through direct recognition of pathogen-associated molecular patterns and damage-associated molecular patterns, PRRs initiate inflammatory responses, including cytokine production, and modulate the adaptive immune response. Ligand binding activates downstream signaling pathways that promote pathogen clearance and drive inflammasome assembly. Accumulating evidence underscores the critical role of PRRs in sensing cellular damage and preserving homeostasis. Importantly, interactions within PRR networks facilitate the formation of multiple PRR-containing inflammasomes (PANoptosome), enabling coordinated inflammatory cell death under combined pathogen-associated molecular pattern and damage-associated molecular pattern stimulation. A comprehensive understanding of these interconnected signaling networks is essential for elucidating the regulation of innate immunity and its implications for disease pathogenesis, particularly in the context of infection and inflammation. This review provides a detailed overview of PRR-ligand recognition, downstream signaling mechanisms, and inflammasome activation, and discusses emerging insights into PRR regulation that hold promise for novel immunotherapeutic interventions.

模式识别受体（PRRs）是先天免疫系统的基础，其功能是通过抑制病原体的复制和限制宿主组织损伤来检测和消除入侵病原体。通过直接识别病原体相关分子模式（PAMPs）和损伤相关分子模式（DAMPs）， PRRs启动炎症反应，包括细胞因子的产生，并调节适应性免疫反应。配体结合激活下游信号通路，促进病原体清除和驱动炎性小体组装。越来越多的证据强调了PRRs在感知细胞损伤和保持体内平衡中的关键作用。重要的是，PRR网络内的相互作用促进了多个含有PRR的炎症小体（PANoptosome）的形成，从而在PAMP和DAMP联合刺激下实现炎症细胞的协调死亡。全面了解这些相互关联的信号网络对于阐明先天免疫的调节及其对疾病发病机制的影响至关重要，特别是在感染和炎症的背景下。这篇综述提供了PRR配体识别、下游信号机制和炎性体激活的详细概述，并讨论了对PRR调控的新见解，这些见解有望为新的免疫治疗干预提供希望。

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引用次数: 0

Cover and caption 封面及标题

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-13 DOI: 10.1016/S1016-8478(25)00067-6

引用次数: 0

Editorial Board Members/Copyright 编辑委员会成员/版权

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-13 DOI: 10.1016/S1016-8478(25)00069-X

引用次数: 0

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