The EMBO JournalPub Date : 2023-12-19DOI: 10.1038/s44318-023-00017-w
Liyang Du, Qinwei Zhu, Zhonghui Lin
{"title":"Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate","authors":"Liyang Du, Qinwei Zhu, Zhonghui Lin","doi":"10.1038/s44318-023-00017-w","DOIUrl":"https://doi.org/10.1038/s44318-023-00017-w","url":null,"abstract":"","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":" 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138961884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2023-12-15DOI: 10.1038/s44318-023-00006-z
Jose M Delgado, Logan Wallace Shepard, Sarah W Lamson, Samantha L Liu, Christopher J Shoemaker
{"title":"The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover","authors":"Jose M Delgado, Logan Wallace Shepard, Sarah W Lamson, Samantha L Liu, Christopher J Shoemaker","doi":"10.1038/s44318-023-00006-z","DOIUrl":"https://doi.org/10.1038/s44318-023-00006-z","url":null,"abstract":"","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"350 3-4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138996844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2023-12-15DOI: 10.1038/s44318-023-00004-1
Joel A. Crossley, W. Allen, Daniel W. Watkins, T. Sabir, S. Radford, Roman Tuma, I. Collinson, Tomas Fessl
{"title":"Dynamic coupling of fast channel gating with slow ATP-turnover underpins protein transport through the Sec translocon","authors":"Joel A. Crossley, W. Allen, Daniel W. Watkins, T. Sabir, S. Radford, Roman Tuma, I. Collinson, Tomas Fessl","doi":"10.1038/s44318-023-00004-1","DOIUrl":"https://doi.org/10.1038/s44318-023-00004-1","url":null,"abstract":"","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"12 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2023-12-15DOI: 10.1038/s44318-023-00013-0
Yanli Dong, Zhuoya Yu, Yue Li, Bo Huang, Qinru Bai, Yiwei Gao, Qihao Chen, Na Li, Lingli He, Yan Zhao
{"title":"Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400","authors":"Yanli Dong, Zhuoya Yu, Yue Li, Bo Huang, Qinru Bai, Yiwei Gao, Qihao Chen, Na Li, Lingli He, Yan Zhao","doi":"10.1038/s44318-023-00013-0","DOIUrl":"https://doi.org/10.1038/s44318-023-00013-0","url":null,"abstract":"","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"27 107","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138998993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2023-12-14DOI: 10.1038/s44318-023-00002-3
S. Wong, Aghil Soman, N. Korolev, Wahyu Surya, Qinming Chen, Wayne Shum, John van Noort, L. Nordenskiöld
{"title":"The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin","authors":"S. Wong, Aghil Soman, N. Korolev, Wahyu Surya, Qinming Chen, Wayne Shum, John van Noort, L. Nordenskiöld","doi":"10.1038/s44318-023-00002-3","DOIUrl":"https://doi.org/10.1038/s44318-023-00002-3","url":null,"abstract":"","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"36 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138971482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2023-12-11DOI: 10.15252/embj.2023113590
Federico Cocozza, Lorena Martin-Jaular, Lien Lippens, Aurelie Di Cicco, Yago A Arribas, Nicolas Ansart, Florent Dingli, Michael Richard, Louise Merle, Mabel Jouve San Roman, Patrick Poullet, Damarys Loew, Daniel Lévy, An Hendrix, George Kassiotis, Alain Joliot, Mercedes Tkach, Clotilde Théry
{"title":"Extracellular vesicles and co-isolated endogenous retroviruses from murine cancer cells differentially affect dendritic cells","authors":"Federico Cocozza, Lorena Martin-Jaular, Lien Lippens, Aurelie Di Cicco, Yago A Arribas, Nicolas Ansart, Florent Dingli, Michael Richard, Louise Merle, Mabel Jouve San Roman, Patrick Poullet, Damarys Loew, Daniel Lévy, An Hendrix, George Kassiotis, Alain Joliot, Mercedes Tkach, Clotilde Théry","doi":"10.15252/embj.2023113590","DOIUrl":"https://doi.org/10.15252/embj.2023113590","url":null,"abstract":"Cells secrete extracellular vesicles (EVs) and non-vesicular extracellular (nano)particles (NVEPs or ENPs) that may play a role in intercellular communication. Tumor-derived EVs have been proposed to induce immune priming of antigen presenting cells or to be immuno-suppressive agents. We suspect that such disparate functions are due to variable compositions in EV subtypes and ENPs. We aimed to characterize the array of secreted EVs and ENPs of murine tumor cell lines. Unexpectedly, we identified virus-like particles (VLPs) from endogenous murine leukemia virus in preparations of EVs produced by many tumor cells. We established a protocol to separate small EVs from VLPs and ENPs. We compared their protein composition and analyzed their functional interaction with target dendritic cells. ENPs were poorly captured and did not affect dendritic cells. Small EVs specifically induced dendritic cell death. A mixed large/dense EV/VLP preparation was most efficient to induce dendritic cell maturation and antigen presentation. Our results call for systematic re-evaluation of the respective proportions and functions of non-viral EVs and VLPs produced by murine tumors and their contribution to tumor progression.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2018-08-01Epub Date: 2018-06-19DOI: 10.15252/embj.201798615
Amandine Viau, Frank Bienaimé, Kamile Lukas, Abhijeet P Todkar, Manuel Knoll, Toma A Yakulov, Alexis Hofherr, Oliver Kretz, Martin Helmstädter, Wilfried Reichardt, Simone Braeg, Tom Aschman, Annette Merkle, Dietmar Pfeifer, Verónica I Dumit, Marie-Claire Gubler, Roland Nitschke, Tobias B Huber, Fabiola Terzi, Jörn Dengjel, Florian Grahammer, Michael Köttgen, Hauke Busch, Melanie Boerries, Gerd Walz, Antigoni Triantafyllopoulou, E Wolfgang Kuehn
{"title":"Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney.","authors":"Amandine Viau, Frank Bienaimé, Kamile Lukas, Abhijeet P Todkar, Manuel Knoll, Toma A Yakulov, Alexis Hofherr, Oliver Kretz, Martin Helmstädter, Wilfried Reichardt, Simone Braeg, Tom Aschman, Annette Merkle, Dietmar Pfeifer, Verónica I Dumit, Marie-Claire Gubler, Roland Nitschke, Tobias B Huber, Fabiola Terzi, Jörn Dengjel, Florian Grahammer, Michael Köttgen, Hauke Busch, Melanie Boerries, Gerd Walz, Antigoni Triantafyllopoulou, E Wolfgang Kuehn","doi":"10.15252/embj.201798615","DOIUrl":"10.15252/embj.201798615","url":null,"abstract":"<p><p>Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2<sup>+</sup> mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis.</p>","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/93/EMBJ-37-e98615.PMC6068446.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36243138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2013-04-03Epub Date: 2013-03-08DOI: 10.1038/emboj.2013.31
Irene Aksoy, Ralf Jauch, Jiaxuan Chen, Mateusz Dyla, Ushashree Divakar, Gireesh K Bogu, Roy Teo, Calista Keow Leng Ng, Wishva Herath, Sun Lili, Andrew P Hutchins, Paul Robson, Prasanna R Kolatkar, Lawrence W Stanton
{"title":"Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.","authors":"Irene Aksoy, Ralf Jauch, Jiaxuan Chen, Mateusz Dyla, Ushashree Divakar, Gireesh K Bogu, Roy Teo, Calista Keow Leng Ng, Wishva Herath, Sun Lili, Andrew P Hutchins, Paul Robson, Prasanna R Kolatkar, Lawrence W Stanton","doi":"10.1038/emboj.2013.31","DOIUrl":"https://doi.org/10.1038/emboj.2013.31","url":null,"abstract":"<p><p>How regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique 'compressed' Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at 'canonical' binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point-mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome.</p>","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":" ","pages":"938-53"},"PeriodicalIF":11.4,"publicationDate":"2013-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/emboj.2013.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31293757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guy Schoehn, Anne Marie Di Guilmi, David Lemaire, Ina Attree, Winfried Weissenhorn, Andréa Dessen
{"title":"Oligomerization of type III secretion proteins PopB and PopD precedes pore formation in Pseudomonas.","authors":"Guy Schoehn, Anne Marie Di Guilmi, David Lemaire, Ina Attree, Winfried Weissenhorn, Andréa Dessen","doi":"10.1093/emboj/cdg499","DOIUrl":"https://doi.org/10.1093/emboj/cdg499","url":null,"abstract":"<p><p>Pseudomonas aeruginosa is the agent of opportunistic infections in immunocompromised individuals and chronic respiratory illnesses in cystic fibrosis patients. Pseudomonas aeruginosa utilizes a type III secretion system for injection of toxins into the host cell cytoplasm through a channel on the target membrane (the 'translocon'). Here, we have functionally and structurally characterized PopB and PopD, membrane proteins implicated in the formation of the P.aeruginosa translocon. PopB and PopD form soluble complexes with their common chaperone, PcrH, either as stable heterodimers or as metastable heterooligomers. Only oligomeric forms are able to bind to and disrupt cholesterol-rich membranes, which occurs within a pH range of 5-7 in the case of PopB/PcrH, and only at acidic pH for PcrH-free PopD. Electron microscopy reveals that upon membrane association PopB and PopD form 80 A wide rings which encircle 40 A wide cavities. Thus, formation of metastable oligomers precedes membrane association and ring generation in the formation of the Pseudomonas translocon, a mechanism which may be similar for other pathogens that employ type III secretion systems.</p>","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":" ","pages":"4957-67"},"PeriodicalIF":11.4,"publicationDate":"2003-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emboj/cdg499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40830801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}