EMBO Reports最新文献_第4页

SOX10 mediates glioblastoma cell-state plasticity. SOX10介导胶质母细胞瘤细胞状态的可塑性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44319-024-00258-8

Ka-Hou Man, Yonghe Wu, Zhenjiang Gao, Anna-Sophie Spreng, Johanna Keding, Jasmin Mangei, Pavle Boskovic, Jan-Philipp Mallm, Hai-Kun Liu, Charles D Imbusch, Peter Lichter, Bernhard Radlwimmer

{"title":"SOX10 mediates glioblastoma cell-state plasticity.","authors":"Ka-Hou Man, Yonghe Wu, Zhenjiang Gao, Anna-Sophie Spreng, Johanna Keding, Jasmin Mangei, Pavle Boskovic, Jan-Philipp Mallm, Hai-Kun Liu, Charles D Imbusch, Peter Lichter, Bernhard Radlwimmer","doi":"10.1038/s44319-024-00258-8","DOIUrl":"10.1038/s44319-024-00258-8","url":null,"abstract":"Phenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5113-5140"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282183","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

Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes. Ehbp1 可将 Wnt/Wingless 有序地分拣到基底侧和顶端细胞膜。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1038/s44319-024-00289-1

Yuan Gao, Jing Feng, Yansong Zhang, Mengyuan Yi, Lebing Zhang, Yan Yan, Alan Jian Zhu, Min Liu

{"title":"Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes.","authors":"Yuan Gao, Jing Feng, Yansong Zhang, Mengyuan Yi, Lebing Zhang, Yan Yan, Alan Jian Zhu, Min Liu","doi":"10.1038/s44319-024-00289-1","DOIUrl":"10.1038/s44319-024-00289-1","url":null,"abstract":"Wingless (Wg)/Wnt signaling plays a critical role in both development and adult tissue homeostasis. In the Drosophila larval wing disc epithelium, the orderly delivery of Wg/Wnt to the apical and basal cell surfaces is essential for wing development. Here, we identified Ehbp1 as the switch that dictates the direction of Wg/Wnt polarized intracellular transport: the Adaptor Protein complex 1 (AP-1) delivers Wg/Wnt to the basolateral cell surface, and its sequestration by Ehbp1 redirects Wg/Wnt for apical delivery. Genetic analyses showed that Ehbp1 specifically regulates the polarized distribution of Wg/Wnt, a process that depends on the dedicated Wg/Wnt cargo receptor Wntless. Mechanistically, Ehbp1 competes with Wntless for AP-1 binding, thereby preventing the unregulated basolateral Wg/Wnt transport. Reducing Ehbp1 expression, or removing the coiled-coil motifs within its bMERB domain, leads to basolateral Wg/Wnt accumulation. Importantly, the regulation of polarized Wnt delivery by EHBP1 is conserved in vertebrates. The generality of this switch mechanism for regulating intracellular transport remains to be determined in future studies.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5053-5079"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460723","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

Robust tissue pattern formation by coupling morphogen signal and cell adhesion. 通过形态发生信号与细胞粘附的耦合，形成稳健的组织模式。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-27 DOI: 10.1038/s44319-024-00261-z

Kosuke Mizuno, Tsuyoshi Hirashima, Satoshi Toda

{"title":"Robust tissue pattern formation by coupling morphogen signal and cell adhesion.","authors":"Kosuke Mizuno, Tsuyoshi Hirashima, Satoshi Toda","doi":"10.1038/s44319-024-00261-z","DOIUrl":"10.1038/s44319-024-00261-z","url":null,"abstract":"Morphogens, locally produced signaling molecules, form a concentration gradient to guide tissue patterning. Tissue patterns emerge as a collaboration between morphogen diffusion and responsive cell behaviors, but the mechanisms through which diffusing morphogens define precise spatial patterns amidst biological fluctuations remain unclear. To investigate how cells respond to diffusing proteins to generate tissue patterns, we develop SYMPLE3D, a 3D culture platform. By engineering gene expression responsive to artificial morphogens, we observe that coupling morphogen signals with cadherin-based adhesion is sufficient to convert a morphogen gradient into distinct tissue domains. Morphogen-induced cadherins gather activated cells into a single domain, removing ectopically activated cells. In addition, we reveal a switch-like induction of cadherin-mediated compaction and cell mixing, homogenizing activated cells within the morphogen gradient to form a uniformly activated domain with a sharp boundary. These findings highlight the cooperation between morphogen gradients and cell adhesion in robust tissue patterning and introduce a novel method for tissue engineering to develop new tissue domains in organoids.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4803-4826"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343800","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

Publisher Correction: Emerging toolkits for decoding the co-occurrence of modified histones and chromatin proteins. 出版商更正：解码修饰组蛋白和染色质蛋白共存的新兴工具包。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00269-5

Anne-Sophie Pepin, Robert Schneider

引用次数: 0

Abundant mRNA m¹A modification in dinoflagellates: a new layer of gene regulation. 甲藻中丰富的 mRNA m1A 修饰：基因调控的新层次。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-02 DOI: 10.1038/s44319-024-00234-2

Chongping Li, Ying Li, Jia Guo, Yuci Wang, Xiaoyan Shi, Yangyi Zhang, Nan Liang, Honghui Ma, Jie Yuan, Jiawei Xu, Hao Chen

{"title":"Abundant mRNA m1A modification in dinoflagellates: a new layer of gene regulation.","authors":"Chongping Li, Ying Li, Jia Guo, Yuci Wang, Xiaoyan Shi, Yangyi Zhang, Nan Liang, Honghui Ma, Jie Yuan, Jiawei Xu, Hao Chen","doi":"10.1038/s44319-024-00234-2","DOIUrl":"10.1038/s44319-024-00234-2","url":null,"abstract":"Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4655-4673"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119264","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

Author Correction: Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice. 作者更正：表达 A152T 人类 tau 会导致转基因小鼠出现年龄依赖性神经元功能障碍和丧失。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00212-8

Sumihiro Maeda, Biljana Djukic, Praveen Taneja, Gui-Qiu Yu, Iris Lo, Allyson Davis, Ryan Craft, Weikun Guo, Xin Wang, Daniel Kim, Ravikumar Ponnusamy, T Michael Gill, Eliezer Masliah, Lennart Mucke

引用次数: 0

Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects. 昆虫中富含脯氨酸的 II 型抗菌肽的活性、结构和多样性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1038/s44319-024-00277-5

Weiping Huang, Chetana Baliga, Elena V Aleksandrova, Gemma Atkinson, Yury S Polikanov, Nora Vázquez-Laslop, Alexander S Mankin

{"title":"Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects.","authors":"Weiping Huang, Chetana Baliga, Elena V Aleksandrova, Gemma Atkinson, Yury S Polikanov, Nora Vázquez-Laslop, Alexander S Mankin","doi":"10.1038/s44319-024-00277-5","DOIUrl":"10.1038/s44319-024-00277-5","url":null,"abstract":"Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough-all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs' C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5194-5211"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460721","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

Publisher Correction: Cytoplasmic FBXO38 mediates PD-1 degradation. 出版商更正：细胞质 FBXO38 介导 PD-1 降解。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00298-0

Xiwei Liu, Xiangbo Meng, Zuomiao Lin, Shutan Jiang, Haifeng Liu, Shao-Cong Sun, Xiaolong Liu, Penghui Zhou, Xiaowu Huang, Lai Wei, Wei Yang, Chenqi Xu

引用次数: 0

SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release. 蛋白磷酸酶 5 的 SUMO 化调节磷酸酶活性和底物释放。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-20 DOI: 10.1038/s44319-024-00250-2

Rebecca A Sager, Sarah J Backe, Diana M Dunn, Jennifer A Heritz, Elham Ahanin, Natela Dushukyan, Barry Panaretou, Gennady Bratslavsky, Mark R Woodford, Dimitra Bourboulia, Mehdi Mollapour

{"title":"SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release.","authors":"Rebecca A Sager, Sarah J Backe, Diana M Dunn, Jennifer A Heritz, Elham Ahanin, Natela Dushukyan, Barry Panaretou, Gennady Bratslavsky, Mark R Woodford, Dimitra Bourboulia, Mehdi Mollapour","doi":"10.1038/s44319-024-00250-2","DOIUrl":"10.1038/s44319-024-00250-2","url":null,"abstract":"The serine/threonine protein phosphatase 5 (PP5) regulates hormone and stress-induced signaling networks. Unlike other phosphoprotein phosphatases, PP5 contains both regulatory and catalytic domains and is further regulated through post-translational modifications (PTMs). Here we identify that SUMOylation of K430 in the catalytic domain of PP5 regulates phosphatase activity. Additionally, phosphorylation of PP5-T362 is pre-requisite for SUMOylation, suggesting the ordered addition of PTMs regulates PP5 function in cells. Using the glucocorticoid receptor, a well known substrate for PP5, we demonstrate that SUMOylation results in substrate release from PP5. We harness this information to create a non-SUMOylatable K430R mutant as a 'substrate trap' and globally identified novel PP5 substrate candidates. Lastly, we generated a consensus dephosphorylation motif using known substrates, and verified its presence in the new candidate substrates. This study unravels the impact of cross talk of SUMOylation and phosphorylation on PP5 phosphatase activity and substrate release in cells.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4636-4654"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282184","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

Kinesin-1 mediates proper ER folding of the Ca_V1.2 channel and maintains mouse glucose homeostasis. 驱动蛋白-1 介导 CaV1.2 通道的正确 ER 折叠并维持小鼠的葡萄糖稳态。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1038/s44319-024-00246-y

Yosuke Tanaka, Atena Farkhondeh, Wenxing Yang, Hitoshi Ueno, Mitsuhiko Noda, Nobutaka Hirokawa

{"title":"Kinesin-1 mediates proper ER folding of the CaV1.2 channel and maintains mouse glucose homeostasis.","authors":"Yosuke Tanaka, Atena Farkhondeh, Wenxing Yang, Hitoshi Ueno, Mitsuhiko Noda, Nobutaka Hirokawa","doi":"10.1038/s44319-024-00246-y","DOIUrl":"10.1038/s44319-024-00246-y","url":null,"abstract":"Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells is a principal mechanism for systemic glucose homeostasis, of which regulatory mechanisms are still unclear. Here we show that kinesin molecular motor KIF5B is essential for GSIS through maintaining the voltage-gated calcium channel CaV1.2 levels, by facilitating an Hsp70-to-Hsp90 chaperone exchange to pass through the quality control in the endoplasmic reticulum (ER). Phenotypic analyses of KIF5B conditional knockout (cKO) mouse beta cells revealed significant abolishment of glucose-stimulated calcium transients, which altered the behaviors of insulin granules via abnormally stabilized cortical F-actin. KIF5B and Hsp90 colocalize to microdroplets on ER sheets, where CaV1.2 but not Kir6.2 is accumulated. In the absence of KIF5B, CaV1.2 fails to be transferred from Hsp70 to Hsp90 via STIP1, and is likely degraded via the proteasomal pathway. KIF5B and Hsc70 overexpression increased CaV1.2 expression via enhancing its chaperone binding. Thus, ER sheets may serve as the place of KIF5B- and Hsp90-dependent chaperone exchange, which predominantly facilitates CaV1.2 production in beta cells and properly enterprises GSIS against diabetes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4777-4802"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343799","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