Communications Biology最新文献_第7页

Stepwise recruitment of chaperone Hsc70 by DNAJB1 produces ordered arrays primed for bursts of amyloid fibril disassembly. DNAJB1对伴侣Hsc70的逐步招募产生有序的阵列，从而引发淀粉样蛋白纤维的断裂分解。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-30 DOI: 10.1038/s42003-025-07906-2

Jim Monistrol, Joseph G Beton, Erin C Johnston, Thi Lieu Dang, Bernd Bukau, Helen R Saibil

{"title":"Stepwise recruitment of chaperone Hsc70 by DNAJB1 produces ordered arrays primed for bursts of amyloid fibril disassembly.","authors":"Jim Monistrol, Joseph G Beton, Erin C Johnston, Thi Lieu Dang, Bernd Bukau, Helen R Saibil","doi":"10.1038/s42003-025-07906-2","DOIUrl":"10.1038/s42003-025-07906-2","url":null,"abstract":"The Hsp70 chaperone system is capable of disassembling pathological aggregates such as amyloid fibres associated with serious degenerative diseases. Here we examine the role of the J-domain protein co-factor in amyloid disaggregation by the Hsc70 system. We used cryo-EM and tomography to compare the assemblies with wild-type DNAJB1 or inactive mutants. We show that DNAJB1 binds regularly along α-synuclein amyloid fibrils and acts in a 2-step recruitment of Hsc70, releasing DNAJB1 auto-inhibition before activating Hsc70 ATPase. The wild-type DNAJB1:Hsc70:Apg2 complex forms dense arrays of chaperones on the fibrils, with Hsc70 on the outer surface. When the auto-inhibition is removed by mutating DNAJB1 (ΔH5 DNAJB1), Hsc70 is recruited to the fibrils at a similar level, but the ΔH5 DNAJB1:Ηsc70:Apg2 complex is inactive, binds less regularly to the fibrils and lacks the ordered clusters. Therefore, we propose that 2-step activation of DNAJB1 regulates the ordered assembly of Hsc70 on the fibril. The localised, dense packing of chaperones could trigger a cascade of recruitment and activation to give coordinated, sequential binding and disaggregation from an exposed fibril end, as previously observed in AFM videos. This mechanism is likely to be important in maintaining a healthy cellular proteome into old age.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"522"},"PeriodicalIF":5.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reference-informed evaluation of batch correction for single-cell omics data with overcorrection awareness. 具有过校正意识的单细胞组学数据批量校正的参考评估。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-30 DOI: 10.1038/s42003-025-07947-7

Xiaoyue Hu, He Li, Ming Chen, Junbin Qian, Hangjin Jiang

{"title":"Reference-informed evaluation of batch correction for single-cell omics data with overcorrection awareness.","authors":"Xiaoyue Hu, He Li, Ming Chen, Junbin Qian, Hangjin Jiang","doi":"10.1038/s42003-025-07947-7","DOIUrl":"10.1038/s42003-025-07947-7","url":null,"abstract":"Batch effect correction (BEC) is fundamental to integrate multiple single-cell RNA sequencing datasets, and its success is critical to empower in-depth interrogation for biological insights. However, no simple metric is available to evaluate BEC performance with sensitivity to data overcorrection, which erases true biological variations and leads to false biological discoveries. Here, we propose RBET, a reference-informed statistical framework for evaluating the success of BEC. Using extensive simulations and six real data examples including scRNA-seq and scATAC-seq datasets with different numbers of batches, batch effect sizes and numbers of cell types, we demonstrate that RBET evaluates the performance of BEC methods more fairly with biologically meaningful insights from data, while other methods may lead to false results. Moreover, RBET is computationally efficient, sensitive to overcorrection and robust to large batch effect sizes. Thus, RBET provides a robust guideline on selecting case-specific BEC method, and the concept of RBET is extendable to other modalities.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"521"},"PeriodicalIF":5.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial transcriptomic profiling of the human fallopian tube epithelium reveals region-specific gene expression patterns. 人类输卵管上皮的空间转录组分析揭示了区域特异性基因表达模式。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07871-w

Jared Sipes, Sagar Rayamajhi, Leonidas E Bantis, Rashna Madan, Amrita Mitra, Rajni V Puri, Mohammod Mahmudur Rahman, Foyez Ahmmed, Harsh B Pathak, Andrew K Godwin

{"title":"Spatial transcriptomic profiling of the human fallopian tube epithelium reveals region-specific gene expression patterns.","authors":"Jared Sipes, Sagar Rayamajhi, Leonidas E Bantis, Rashna Madan, Amrita Mitra, Rajni V Puri, Mohammod Mahmudur Rahman, Foyez Ahmmed, Harsh B Pathak, Andrew K Godwin","doi":"10.1038/s42003-025-07871-w","DOIUrl":"10.1038/s42003-025-07871-w","url":null,"abstract":"The fallopian tube (FT) plays a crucial role in fertility, gynecological health, and high-grade serous ovarian cancer (HGSOC) development. Despite its importance, the spatial transcriptome of the FT's distinct anatomical regions (fimbria, infundibulum, ampulla, and isthmus) remains underexplored. Using the GeoMx Digital Spatial Profiler (DSP) and a targeted ~1800 gene panel, we analyze premenopausal FT epithelium, identifying region-specific gene expression patterns. Our analysis reveals upregulation of mature ciliated cell markers (FOXJ1, MLF1, SPA17, and CTSS) approaching the fimbria, elevated ROS and apoptosis-related transcripts (TXNIP, PRDX5, BAD, GAS1) in the distal FT, and a switch in cell-cell adhesion transcripts (CDH1, CDH3) along the distal-to-proximal axis. We also provide evidence that MHC-II transcripts in the FT are differentially regulated throughout the menstrual cycle, with lower expression in follicular phase. These results suggest spatially regulated expression of FT transcripts with implications for fertilization and early neoplastic changes contributing to HGSOC.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"520"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Humerus shape evolved in cetaceans under relaxed selection and random drift. 鲸类动物的肱骨形状是在随意选择和随机漂移的条件下进化而来的。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07952-w

Maria Ghazali, Svitozar Davydenko, Valeriia Telizhenko, Pavlo Otriazhyi, Karina Vishnyakova, Maia Bukhsianidze, Azucena Solis-Añorve, Igor Dzeverin, Pavel Gol'din

{"title":"Humerus shape evolved in cetaceans under relaxed selection and random drift.","authors":"Maria Ghazali, Svitozar Davydenko, Valeriia Telizhenko, Pavlo Otriazhyi, Karina Vishnyakova, Maia Bukhsianidze, Azucena Solis-Añorve, Igor Dzeverin, Pavel Gol'din","doi":"10.1038/s42003-025-07952-w","DOIUrl":"10.1038/s42003-025-07952-w","url":null,"abstract":"Mammalian humerus shape is mostly predicted by loading. This constraint is lifted for cetaceans and, therefore, can reflect other, specific evolutionary trends. To test this hypothesis, the three-dimensional shape of the humerus for 36 taxa of extinct and extant cetaceans was analyzed. The shape variance concurs with the evolution of diverging baleen and toothed whales and is independent of allometry. It shows traits associated with aquatic locomotion: humeral head twist, diaphysis shortening and straightening, and epiphyses enlargement. Also, changes in the anatomy of the humeral head and greater tubercle, modularity and integration patterns are associated with phylogeny. We suggest relaxed negative selection and random drift as the likely main evolutionary patterns for the evolution of the humerus shape. The evolution of genes regulating the humerus shape corresponds to the anatomical transformations and shows relaxed selection, site-level positive selection and nonsense mutations in cetaceans. Overall, the observed pattern well illustrates a \"fly in a tube model\" and shows its importance as a framework of emerging evolutionary innovations.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"518"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variations in neuronal cytoskeletal integrity affect directed communication in distributed networks during inhibitory control. 在抑制控制期间，神经元细胞骨架完整性的变化影响分布式网络中的定向通信。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07974-4

Julia Elmers, Moritz Mückschel, Katja Akgün, Tjalf Ziemssen, Christian Beste

{"title":"Variations in neuronal cytoskeletal integrity affect directed communication in distributed networks during inhibitory control.","authors":"Julia Elmers, Moritz Mückschel, Katja Akgün, Tjalf Ziemssen, Christian Beste","doi":"10.1038/s42003-025-07974-4","DOIUrl":"10.1038/s42003-025-07974-4","url":null,"abstract":"To ensure goal-directed behavior in daily life, the use of inhibitory control is of great importance. The aim of this study is to shed light on the underlying neuronal mechanisms of inhibitory control and the relevance of cytoarchitectonic integrity in it. We combine sophisticated EEG analysis techniques assessing directed communication between brain structures with measurements of neurofilaments as an index of cytoarchitectonic integrity. We show that an extensive theta band activity related neural network with fronto-temporal, parietal, and occipital brain regions is active during response inhibition. Importantly, cytoarchitectonic integrity as measured using neurofilaments modulates nonlinear directional connectivity, particularly when complex reconfiguration of perceptual and action mapping is required. The study thus shows an inter-relation between different levels of biological functioning-the level of cytoarchitectonic integrity and neurophysiological directed communication-for inhibitory control and emphasizes the role of nonlinear brain connectivity in cognitive control.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"516"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing nucleotide sequence representations in genomic analysis with contrastive optimization. 利用对比优化增强基因组分析中的核苷酸序列表征。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07902-6

Mohammadsaleh Refahi, Bahrad A Sokhansanj, Joshua C Mell, James R Brown, Hyunwoo Yoo, Gavin Hearne, Gail L Rosen

{"title":"Enhancing nucleotide sequence representations in genomic analysis with contrastive optimization.","authors":"Mohammadsaleh Refahi, Bahrad A Sokhansanj, Joshua C Mell, James R Brown, Hyunwoo Yoo, Gavin Hearne, Gail L Rosen","doi":"10.1038/s42003-025-07902-6","DOIUrl":"10.1038/s42003-025-07902-6","url":null,"abstract":"Analysis of genomic and metagenomic sequences is inherently more challenging than that of amino acid sequences due to the higher divergence among evolutionarily related nucleotide sequences, variable k-mer and codon usage within and among genomes of diverse species, and poorly understood selective constraints. We introduce Scorpio (Sequence Contrastive Optimization for Representation and Predictive Inference on DNA), a versatile framework designed for nucleotide sequences that employ contrastive learning to improve embeddings. By leveraging pre-trained genomic language models and k-mer frequency embeddings, Scorpio demonstrates competitive performance in diverse applications, including taxonomic and gene classification, antimicrobial resistance (AMR) gene identification, and promoter detection. A key strength of Scorpio is its ability to generalize to novel DNA sequences and taxa, addressing a significant limitation of alignment-based methods. Scorpio has been tested on multiple datasets with DNA sequences of varying lengths (long and short) and shows robust inference capabilities. Additionally, we provide an analysis of the biological information underlying this representation, including correlations between codon adaptation index as a gene expression factor, sequence similarity, and taxonomy, as well as the functional and structural information of genes.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"517"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing archaeal research through FAIR resource and data sharing, and inclusive community building. 通过公平资源和数据共享以及包容性社区建设推进古细菌研究。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07962-8

Solenne Ithurbide, Nicole Buan, Stefan Schulze

{"title":"Advancing archaeal research through FAIR resource and data sharing, and inclusive community building.","authors":"Solenne Ithurbide, Nicole Buan, Stefan Schulze","doi":"10.1038/s42003-025-07962-8","DOIUrl":"10.1038/s42003-025-07962-8","url":null,"abstract":"Over the last two decades archaeal research has expanded into a wide-ranging research field, driven by a fairly small research community. Archaea are now recognized as important players in the One-Health approach and expertise on the biology of archaea has become crucial in the study of a broad range of topics and environments, including the host-associated microbiomes, major nutrient cycles, greenhouse gas metabolism, the cell biology and origin of eukaryotes, adaptation of life to extremes, as well as various biotechnological applications. Here, we summarize existing resources and ongoing efforts in the engaged broader archaeal scientific community to accelerate research and resource sharing guided by FAIR (findable, accessible, interoperable, reusable) data-sharing principles. We highlight ongoing community efforts that: (i) aim to share protocols and best practices for working with archaea (e.g. ARCHAEA.bio), (ii) combine large 'omics datasets for the dissemination of unified, system-wide results (e.g. Archaeal Proteome Project, KBase) and (iii) provide opportunities for scientists to present their work in a supportive environment and to forge connections and collaborations (e.g. Archaea Power Hour). Together, these resources and projects promise to spur and cross-fertilize research, making archaeal research more accessible to a broader and more diverse audience.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"519"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular osmolarity regulates osteoblast migration through the TRPV4-Rho/ROCK signaling. 细胞外渗透压通过TRPV4-Rho/ROCK信号调控成骨细胞迁移。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-29 DOI: 10.1038/s42003-025-07946-8

Yijie Li, Yanyan Yang, Xiaohuan Wang, Long Li, Mouwang Zhou

{"title":"Extracellular osmolarity regulates osteoblast migration through the TRPV4-Rho/ROCK signaling.","authors":"Yijie Li, Yanyan Yang, Xiaohuan Wang, Long Li, Mouwang Zhou","doi":"10.1038/s42003-025-07946-8","DOIUrl":"10.1038/s42003-025-07946-8","url":null,"abstract":"For precise bone formation, osteoblasts need to accurately migrate to specific sites guided by various biochemical and mechanical cues. During this migration, fluctuations in extracellular osmolarity may arise from shifts in the surrounding fluid environment. However, as a main regulator of cell morphology and function, whether the extracellular osmolarity change may affect osteoblast migration remains unclear. Here, we provide evidence showing that changes in extracellular osmolarity significantly impact osteoblast migration, with a hypotonic environment enhancing it while a hypertonic environment inhibiting it. Further, our findings reveal that a hypotonic treatment increases intracellular pressure, activating the Transient Receptor Potential Vanilloid 4 (TRPV4) channel. This activation of TRPV4 modulates stress fibers, focal adhesions (FAs), and cell polarity through the Rho/ROCK signaling pathway, ultimately impacting osteoblast migration. Our findings provide valuable insights into the significant influence of extracellular osmolarity on osteoblast migration, which has potential implications for enhancing our understanding of bone remodeling.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"515"},"PeriodicalIF":5.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Haptophyte-infecting viruses change the genome condensing proteins of dinoflagellates. 接触虫感染病毒改变鞭毛藻的基因组凝聚蛋白。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-28 DOI: 10.1038/s42003-025-07905-3

Haina Wang, Lingjie Meng, Sara Otaegi-Ugartemendia, Gabriela Nérida Condezo, Romain Blanc-Mathieu, Runar Stokke, Marius Rydningen Langvad, David Brandt, Jörn Kalinowski, Håkon Dahle, Carmen San Martín, Hiroyuki Ogata, Ruth-Anne Sandaa

{"title":"Haptophyte-infecting viruses change the genome condensing proteins of dinoflagellates.","authors":"Haina Wang, Lingjie Meng, Sara Otaegi-Ugartemendia, Gabriela Nérida Condezo, Romain Blanc-Mathieu, Runar Stokke, Marius Rydningen Langvad, David Brandt, Jörn Kalinowski, Håkon Dahle, Carmen San Martín, Hiroyuki Ogata, Ruth-Anne Sandaa","doi":"10.1038/s42003-025-07905-3","DOIUrl":"10.1038/s42003-025-07905-3","url":null,"abstract":"Giant viruses are extraordinary members of the virosphere due to their structural complexity and high diversity in gene content. Haptophytes are ecologically important primary producers in the ocean, and all known viruses that infect haptophytes are giant viruses. However, little is known about the specifics of their infection cycles and the responses they trigger in their host cells. Our in-depth electron microscopic, phylogenomic and virion proteomic analyses of two haptophyte-infecting giant viruses, Haptolina ericina virus RF02 (HeV RF02) and Prymnesium kappa virus RF02 (PkV RF02), unravel their large capacity for host manipulation and arsenals that function during the infection cycle from virus entry to release. The virus infection induces significant morphological changes in the host cell that is manipulated to build a virus proliferation factory. Both viruses' genomes encode a putative nucleoprotein (dinoflagellate/viral nucleoprotein; DVNP), which was also found in the virion proteome of PkV RF02. Phylogenetic analysis suggests that DVNPs are widespread in marine giant metaviromes. Furthermore, the analysis shows that the dinoflagellate homologues were possibly acquired from viruses of the order Imitervirales. These findings enhance our understanding of how viruses impact the biology of microalgae, providing insights into evolutionary biology, ecosystem dynamics, and nutrient cycling in the ocean.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"510"},"PeriodicalIF":5.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The small molecule ML233 is a direct inhibitor of tyrosinase function. 小分子 ML233 是酪氨酸酶功能的直接抑制剂。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-28 DOI: 10.1038/s42003-025-07973-5

Romain Menard, Aissette Baanannou, Caroline Halluin, Dexter Morse, Sadie Kuhn, Joel H Graber, James Strickland, Romain Madelaine

{"title":"The small molecule ML233 is a direct inhibitor of tyrosinase function.","authors":"Romain Menard, Aissette Baanannou, Caroline Halluin, Dexter Morse, Sadie Kuhn, Joel H Graber, James Strickland, Romain Madelaine","doi":"10.1038/s42003-025-07973-5","DOIUrl":"10.1038/s42003-025-07973-5","url":null,"abstract":"Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. However, despite decades of research, currently there is no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report the characterization of the ML233 chemical as a potent inhibitor of tyrosinase activity in vivo and in vitro. We demonstrate that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also predict that these effects are mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. Together, our results reveal that ML233 plays roles in both healthy and pathological skin cells via inhibition of melanin production. ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"506"},"PeriodicalIF":5.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0