EMBO Reports最新文献_第9页

A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets. 一种新型细菌效应蛋白介导 ER-LD 膜接触以调节宿主脂滴。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-09-27 DOI: 10.1038/s44319-024-00266-8

Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk

{"title":"A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets.","authors":"Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk","doi":"10.1038/s44319-024-00266-8","DOIUrl":"10.1038/s44319-024-00266-8","url":null,"abstract":"<p><p>Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER). Here, we identify a novel bacterial effector protein, CbEPF1, which acts as a molecular tether beyond the confines of the BCV and facilitates interactions between host cell organelles. Coxiella burnetii, an obligate intracellular bacterial pathogen, encodes the FFAT motif-containing protein CbEPF1 which localizes to host lipid droplets (LDs). CbEPF1 establishes inter-organelle contact sites between host LDs and the ER through its interactions with VAP family proteins. Intriguingly, CbEPF1 modulates growth of host LDs in a FFAT motif-dependent manner. These findings highlight the potential for bacterial effector proteins to impact host cellular homeostasis by manipulating inter-organelle communication beyond conventional BCVs.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343796","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

miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity. miRNA 介导的 gephyrin 合成控制驱动持续的抑制性突触可塑性。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-18 DOI: 10.1038/s44319-024-00253-z

Theresa M Welle,Dipen Rajgor,Dean J Kareemo,Joshua D Garcia,Sarah M Zych,Sarah E Wolfe,Sara E Gookin,Tyler P Martinez,Mark L Dell'Acqua,Christopher P Ford,Matthew J Kennedy,Katharine R Smith

{"title":"miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.","authors":"Theresa M Welle,Dipen Rajgor,Dean J Kareemo,Joshua D Garcia,Sarah M Zych,Sarah E Wolfe,Sara E Gookin,Tyler P Martinez,Mark L Dell'Acqua,Christopher P Ford,Matthew J Kennedy,Katharine R Smith","doi":"10.1038/s44319-024-00253-z","DOIUrl":"https://doi.org/10.1038/s44319-024-00253-z","url":null,"abstract":"Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"38 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248383","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

Reduction of chromosomal instability and inflammation is a common aspect of adaptation to aneuploidy. 减少染色体不稳定性和炎症是适应非整倍体的一个常见方面。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-18 DOI: 10.1038/s44319-024-00252-0

Dorine C Hintzen,Michael Schubert,Mar Soto,René H Medema,Jonne A Raaijmakers

{"title":"Reduction of chromosomal instability and inflammation is a common aspect of adaptation to aneuploidy.","authors":"Dorine C Hintzen,Michael Schubert,Mar Soto,René H Medema,Jonne A Raaijmakers","doi":"10.1038/s44319-024-00252-0","DOIUrl":"https://doi.org/10.1038/s44319-024-00252-0","url":null,"abstract":"Aneuploidy, while detrimental to untransformed cells, is notably prevalent in cancer. Aneuploidy is found as an early event during tumorigenesis which indicates that cancer cells have the ability to surmount the initial stress responses associated with aneuploidy, enabling rapid proliferation despite aberrant karyotypes. To generate more insight into key cellular processes and requirements underlying adaptation to aneuploidy, we generated a panel of aneuploid clones in p53-deficient RPE-1 cells and studied their behavior over time. As expected, de novo-generated aneuploid clones initially display reduced fitness, enhanced levels of chromosomal instability (CIN), and an upregulated inflammatory response. Intriguingly, after prolonged culturing, aneuploid clones exhibit increased proliferation rates while maintaining aberrant karyotypes, indicative of an adaptive response to the aneuploid state. Interestingly, all adapted clones display reduced CIN and reduced inflammatory signaling, suggesting that these are common aspects of adaptation to aneuploidy. Collectively, our data suggests that CIN and concomitant inflammation are key processes that require correction to allow for fast proliferation in vitro. Finally, we provide evidence that amplification of oncogenic KRAS can promote adaptation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"19 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248384","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

Amplified centrosomes-more than just a threat. 扩增的中心体--不仅仅是威胁

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-16 DOI: 10.1038/s44319-024-00260-0

Eva Kiermaier,Isabel Stötzel,Marina A Schapfl,Andreas Villunger

{"title":"Amplified centrosomes-more than just a threat.","authors":"Eva Kiermaier,Isabel Stötzel,Marina A Schapfl,Andreas Villunger","doi":"10.1038/s44319-024-00260-0","DOIUrl":"https://doi.org/10.1038/s44319-024-00260-0","url":null,"abstract":"Centrosomes are major organizing components of the tubulin-based cytoskeleton. In recent years, we have gained extensive knowledge about their structure, biogenesis, and function from single cells, cell-cell interactions to tissue homeostasis, including their role in human diseases. Centrosome abnormalities are linked to, among others primary microcephaly, birth defects, ciliopathies, and tumorigenesis. Centrosome amplification, a state where two or more centrosomes are present in the G1 phase of the cell cycle, correlates in cancer with karyotype alterations, clinical aggressiveness, and lymph node metastasis. However, amplified centrosomes also appear in healthy tissues and, independent of their established role, in multi-ciliation. One example is the liver where hepatocytes carry amplified centrosomes owing to whole-genome duplication events during organogenesis. More recently, amplified centrosomes have been found in neuronal progenitors and several cell types of hematopoietic origin in which they enhance cellular effector functions. These findings suggest that extra centrosomes do not necessarily pose a risk for genome integrity and are harnessed for physiological processes. Here, we compare established and emerging 'non-canonical functions' of amplified centrosomes in cancerous and somatic cells and discuss their role in cellular physiology.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"5 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248385","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

RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation. RNF144B 通过靶向 MDA5 进行自噬降解来负向调节抗病毒免疫。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-16 DOI: 10.1038/s44319-024-00256-w

Guoxiu Li,Jing Zhang,Zhixun Zhao,Jian Wang,Jiaoyang Li,Weihong Xu,Zhanding Cui,Pu Sun,Hong Yuan,Tao Wang,Kun Li,Xingwen Bai,Xueqing Ma,Pinghua Li,Yuanfang Fu,Yimei Cao,Huifang Bao,Dong Li,Zaixin Liu,Ning Zhu,Lijie Tang,Zengjun Lu

引用次数: 0

Biochemical curiosities : Piquing students' interest in biochemistry by exploring evolution's pursuit of the improbable. 生化奇观：通过探索进化对不可能的追求，激发学生对生物化学的兴趣。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-13 DOI: 10.1038/s44319-024-00259-7

Sunil Laxman

引用次数: 0

HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells. HPV-YAP1 致癌联盟驱动输卵管上皮细胞恶性转化。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-13 DOI: 10.1038/s44319-024-00233-3

Chunbo He,Xiangmin Lv,Jiyuan Liu,Jinpeng Ruan,Peichao Chen,Cong Huang,Peter C Angeletti,Guohua Hua,Madelyn Leigh Moness,Davie Shi,Anjali Dhar,Siyi Yang,Savannah Murphy,Isabelle Montoute,Xingcheng Chen,Kazi Nazrul Islam,Sophia George,Tan A Ince,Ronny Drapkin,Chittibabu Guda,John S Davis,Cheng Wang

{"title":"HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells.","authors":"Chunbo He,Xiangmin Lv,Jiyuan Liu,Jinpeng Ruan,Peichao Chen,Cong Huang,Peter C Angeletti,Guohua Hua,Madelyn Leigh Moness,Davie Shi,Anjali Dhar,Siyi Yang,Savannah Murphy,Isabelle Montoute,Xingcheng Chen,Kazi Nazrul Islam,Sophia George,Tan A Ince,Ronny Drapkin,Chittibabu Guda,John S Davis,Cheng Wang","doi":"10.1038/s44319-024-00233-3","DOIUrl":"https://doi.org/10.1038/s44319-024-00233-3","url":null,"abstract":"High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"3 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248387","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

3R centres contributions to change animal experimentation : A field report from Charité 3R, the 3R centre of a medical faculty. 3R 中心对改变动物实验的贡献：来自 Charité 3R（一个医学院的 3R 中心）的实地报告。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-13 DOI: 10.1038/s44319-024-00262-y

Ida Retter,Laura Behm,Lisa Grohmann,Karin Schmelz,Jennifer Rosowski,Stefan Hippenstiel

引用次数: 0

Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice. 谷氨酰胺溶解为调节小鼠破骨细胞分化提供了核苷酸和氨基酸。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-13 DOI: 10.1038/s44319-024-00255-x

Guoli Hu,Yilin Yu,Yinshi Ren,Robert J Tower,Guo-Fang Zhang,Courtney M Karner

{"title":"Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice.","authors":"Guoli Hu,Yilin Yu,Yinshi Ren,Robert J Tower,Guo-Fang Zhang,Courtney M Karner","doi":"10.1038/s44319-024-00255-x","DOIUrl":"https://doi.org/10.1038/s44319-024-00255-x","url":null,"abstract":"Osteoclasts are bone resorbing cells that are essential to maintain skeletal integrity and function. While many of the growth factors and molecular signals that govern osteoclastogenesis are well studied, how the metabolome changes during osteoclastogenesis is unknown. Using a multifaceted approach, we identified a metabolomic signature of osteoclast differentiation consisting of increased amino acid and nucleotide metabolism. Maintenance of the osteoclast metabolic signature is governed by elevated glutaminolysis. Mechanistically, glutaminolysis provides amino acids and nucleotides which are essential for osteoclast differentiation and bone resorption in vitro. Genetic experiments in mice found that glutaminolysis is essential for osteoclastogenesis and bone resorption in vivo. Highlighting the therapeutic implications of these findings, inhibiting glutaminolysis using CB-839 prevented ovariectomy induced bone loss in mice. Collectively, our data provide strong genetic and pharmacological evidence that glutaminolysis is essential to regulate osteoclast metabolism, promote osteoclastogenesis and modulate bone resorption in mice.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"1 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248386","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

FBXO38 is dispensable for PD-1 regulation. FBXO38 对于 PD-1 的调控是必不可少的。

IF 7.7 1区生物学

EMBO Reports Pub Date : 2024-09-12 DOI: 10.1038/s44319-024-00220-8

Nikol Dibus,Eva Salyova,Karolina Kolarova,Alikhan Abdirov,Michele Pagano,Ondrej Stepanek,Lukas Cermak

引用次数: 0