EMBO Journal最新文献_第7页

Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer. 大核细胞介导三阴性乳腺癌对谷氨酰胺转运损失的抵抗。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-17 DOI: 10.1038/s44318-024-00271-6

Kanu Wahi, Natasha Freidman, Qian Wang, Michelle Devadason, Lake-Ee Quek, Angel Pang, Larissa Lloyd, Mark Larance, Fabio Zanini, Kate Harvey, Sandra O'Toole, Yi Fang Guan, Jeff Holst

{"title":"Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer.","authors":"Kanu Wahi, Natasha Freidman, Qian Wang, Michelle Devadason, Lake-Ee Quek, Angel Pang, Larissa Lloyd, Mark Larance, Fabio Zanini, Kate Harvey, Sandra O'Toole, Yi Fang Guan, Jeff Holst","doi":"10.1038/s44318-024-00271-6","DOIUrl":"https://doi.org/10.1038/s44318-024-00271-6","url":null,"abstract":"Triple-negative breast cancer (TNBC) metabolism and cell growth uniquely rely on glutamine uptake by the transporter ASCT2. Despite previous data reporting cell growth inhibition after ASCT2 knockdown, we here show that ASCT2 CRISPR knockout is tolerated by TNBC cell lines. Despite the loss of a glutamine transporter and low rate of glutamine uptake, intracellular glutamine steady-state levels were increased in ASCT2 knockout compared to control cells. Proteomics analysis revealed upregulation of macropinocytosis, reduction in glutamine efflux and increased glutamine synthesis in ASCT2 knockout cells. Deletion of ASCT2 in the TNBC cell line HCC1806 induced a strong increase in macropinocytosis across five ASCT2 knockout clones, compared to a modest increase in ASCT2 knockdown. In contrast, ASCT2 knockout impaired cell proliferation in the non-macropinocytic HCC1569 breast cancer cells. These data identify macropinocytosis as a critical secondary glutamine acquisition pathway in TNBC and a novel resistance mechanism to strategies targeting glutamine uptake alone. Despite this adaptation, TNBC cells continue to rely on glutamine metabolism for their growth, providing a rationale for targeting of more downstream glutamine metabolism components.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Complement-mediated killing of Escherichia coli by mechanical destabilization of the cell envelope. 通过机械方式破坏细胞膜的稳定性，以补体为媒介杀死大肠杆菌。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-14 DOI: 10.1038/s44318-024-00266-3

Georgina Benn, Christian Bortolini, David M Roberts, Alice L B Pyne, Séamus Holden, Bart W Hoogenboom

引用次数: 0

Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay. mRNA 脱烯酰化率模型揭示了 mRNA 脱烯酰化与衰变之间的复杂关系。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-11 DOI: 10.1038/s44318-024-00258-3

Agnieszka Czarnocka-Cieciura, Jarosław Poznański, Matti Turtola, Rafał Tomecki, Paweł S Krawczyk, Seweryn Mroczek, Wiktoria Orzeł, Upasana Saha, Torben Heick Jensen, Andrzej Dziembowski, Agnieszka Tudek

{"title":"Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay.","authors":"Agnieszka Czarnocka-Cieciura, Jarosław Poznański, Matti Turtola, Rafał Tomecki, Paweł S Krawczyk, Seweryn Mroczek, Wiktoria Orzeł, Upasana Saha, Torben Heick Jensen, Andrzej Dziembowski, Agnieszka Tudek","doi":"10.1038/s44318-024-00258-3","DOIUrl":"https://doi.org/10.1038/s44318-024-00258-3","url":null,"abstract":"Complete cytoplasmic polyadenosine tail (polyA-tail) deadenylation is thought to be essential for initiating mRNA decapping and subsequent degradation. To investigate this prevalent model, we conducted direct RNA sequencing of S. cerevisiae mRNAs derived from chase experiments under steady-state and stress condition. Subsequently, we developed a numerical model based on a modified gamma distribution function, which estimated the transcriptomic deadenylation rate at 10 A/min. A simplified independent method, based on the delineation of quantile polyA-tail values, showed a correlation between the decay and deadenylation rates of individual mRNAs, which appeared consistent within functional transcript groups and associated with codon optimality. Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40% of the transcriptome, singled out this transcript group. While deadenylation and decay of RPG mRNAs accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating the onset of decapping, while also demonstrating complex relations between these processes.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding local immunity to enable regionalized medicine. 了解当地免疫力，实现区域化医疗。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-09 DOI: 10.1038/s44318-024-00255-6

Marco De Giovanni, Donato Inverso, Matteo Iannacone

引用次数: 0

Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging. 哺乳动物大脑的纵向自噬图谱显示，在整个健康衰老过程中都存在持续的有丝分裂。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-04 DOI: 10.1038/s44318-024-00241-y

Anna Rappe, Helena A Vihinen, Fumi Suomi, Antti J Hassinen, Homa Ehsan, Eija S Jokitalo, Thomas G McWilliams

{"title":"Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging.","authors":"Anna Rappe, Helena A Vihinen, Fumi Suomi, Antti J Hassinen, Homa Ehsan, Eija S Jokitalo, Thomas G McWilliams","doi":"10.1038/s44318-024-00241-y","DOIUrl":"10.1038/s44318-024-00241-y","url":null,"abstract":"Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-related neurodegenerative disorders such as Parkinson's and Alzheimer's disease. While mitophagy decreases throughout the lifespan of short-lived model organisms, it remains unknown whether such a decline occurs in the aging mammalian brain-a question of fundamental importance for understanding cell type- and region-specific susceptibility to neurodegeneration. Here, we define the longitudinal dynamics of basal mitophagy and macroautophagy across neuronal and non-neuronal cell types within the intact aging mouse brain in vivo. Quantitative profiling of reporter mouse cohorts from young to geriatric ages reveals cell- and tissue-specific alterations in mitophagy and macroautophagy between distinct subregions and cell populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia and interneurons. We also find that healthy aging is hallmarked by the dynamic accumulation of differentially acidified lysosomes in several neural cell subsets. Our findings argue against any widespread age-related decline in mitophagic activity, instead demonstrating dynamic fluctuations in mitophagy across the aging trajectory, with strong implications for ongoing theragnostic development.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A regulatory module mediating temperature control of cell-cell communication facilitates tree bud dormancy release. 介导细胞间通信温度控制的调节模块有助于树芽休眠的解除。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-03 DOI: 10.1038/s44318-024-00256-5

Shashank K Pandey, Jay Prakash Maurya, Bibek Aryal, Kamil Drynda, Aswin Nair, Pal Miskolczi, Rajesh Kumar Singh, Xiaobin Wang, Yujiao Ma, Tatiana de Souza Moraes, Emmanuelle M Bayer, Etienne Farcot, George W Bassel, Leah R Band, Rishikesh P Bhalerao

{"title":"A regulatory module mediating temperature control of cell-cell communication facilitates tree bud dormancy release.","authors":"Shashank K Pandey, Jay Prakash Maurya, Bibek Aryal, Kamil Drynda, Aswin Nair, Pal Miskolczi, Rajesh Kumar Singh, Xiaobin Wang, Yujiao Ma, Tatiana de Souza Moraes, Emmanuelle M Bayer, Etienne Farcot, George W Bassel, Leah R Band, Rishikesh P Bhalerao","doi":"10.1038/s44318-024-00256-5","DOIUrl":"https://doi.org/10.1038/s44318-024-00256-5","url":null,"abstract":"The control of cell-cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. The LIM1-GA module mediates low temperature-induced plasmodesmata opening, by negatively regulating callose accumulation to promote dormancy release. LIM1 also activates expression of FT1 (FLOWERING LOCUS T), another LT-induced factor, with LIM1-FT1 forming a coherent feedforward loop converging on low-temperature regulation of gibberellin signaling in dormancy release. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell-cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mouse models to investigate in situ cell fate decisions induced by p53. 研究 p53 诱导的原位细胞命运决定的小鼠模型。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-08-19 DOI: 10.1038/s44318-024-00189-z

Elizabeth Lieschke, Annabella F Thomas, Andrew Kueh, Georgia K Atkin-Smith, Pedro L Baldoni, John E La Marca, Savannah Young, Allan Shuai Huang, Aisling M Ross, Lauren Whelan, Deeksha Kaloni, Lin Tai, Gordon K Smyth, Marco J Herold, Edwin D Hawkins, Andreas Strasser, Gemma L Kelly

{"title":"Mouse models to investigate in situ cell fate decisions induced by p53.","authors":"Elizabeth Lieschke, Annabella F Thomas, Andrew Kueh, Georgia K Atkin-Smith, Pedro L Baldoni, John E La Marca, Savannah Young, Allan Shuai Huang, Aisling M Ross, Lauren Whelan, Deeksha Kaloni, Lin Tai, Gordon K Smyth, Marco J Herold, Edwin D Hawkins, Andreas Strasser, Gemma L Kelly","doi":"10.1038/s44318-024-00189-z","DOIUrl":"10.1038/s44318-024-00189-z","url":null,"abstract":"Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. Also, the context-dependent interaction partners and binding loci of p53 remain largely elusive. To be able to examine these questions, we here developed knock-in mice expressing triple-FLAG-tagged p53 to facilitate p53 pull-down and two p53 response reporter mice, knocking tdTomato and GFP into the Puma/Bbc3 and p21 gene loci, respectively. By crossing these reporter mice into a p53-deficient background, we show that the new reporters reliably inform on p53-dependent and p53-independent initiation of both apoptotic or cell cycle arrest/senescence programs, respectively, in vitro and in vivo.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4406-4436"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005776","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

Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy. 重新评估肥厚型心肌病肌球蛋白突变导致的过度收缩统一假说。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-08-27 DOI: 10.1038/s44318-024-00199-x

James A Spudich, Neha Nandwani, Julien Robert-Paganin, Anne Houdusse, Kathleen M Ruppel

引用次数: 0

Author Correction: BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation. 作者更正：含 BCL7A 的 SWI/SNF/BAF 复合物在神经祖细胞分化过程中调节线粒体生物能。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-01 DOI: 10.1038/s44318-024-00157-7

Lena Wischhof, Hang-Mao Lee, Janine Tutas, Clemens Overkott, Eileen Tedt, Miriam Stork, Michael Peitz, Oliver Brüstle, Thomas Ulas, Kristian Händler, Joachim L Schultze, Dan Ehninger, Pierluigi Nicotera, Paolo Salomoni, Daniele Bano

引用次数: 0

Structure of tetrameric forms of the serotonin-gated 5-HT3_A receptor ion channel. 羟色胺门控 5-HT3A 受体离子通道的四聚体结构。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI: 10.1038/s44318-024-00191-5

Bianca Introini, Wenqiang Cui, Xiaofeng Chu, Yingyi Zhang, Ana Catarina Alves, Luise Eckhardt-Strelau, Sabrina Golusik, Menno Tol, Horst Vogel, Shuguang Yuan, Mikhail Kudryashev

{"title":"Structure of tetrameric forms of the serotonin-gated 5-HT3A receptor ion channel.","authors":"Bianca Introini, Wenqiang Cui, Xiaofeng Chu, Yingyi Zhang, Ana Catarina Alves, Luise Eckhardt-Strelau, Sabrina Golusik, Menno Tol, Horst Vogel, Shuguang Yuan, Mikhail Kudryashev","doi":"10.1038/s44318-024-00191-5","DOIUrl":"10.1038/s44318-024-00191-5","url":null,"abstract":"Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography. The tetrameric structures have near-symmetric transmembrane domains, and asymmetric extracellular domains, and can bind serotonin molecules. Computer simulations, based on our cryo-EM structures, were used to decipher the assembly pathway of pentameric 5-HT3R and suggest a potential functional role for the tetrameric receptors.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4451-4471"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134356","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