EMBO Journal最新文献

Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes. Rab2A 介导的高尔基体-脂滴相互作用支持肝细胞分泌极低密度脂蛋白。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-04 DOI: 10.1038/s44318-024-00288-x

Min Xu, Zi-Yue Chen, Yang Li, Yue Li, Ge Guo, Rong-Zheng Dai, Na Ni, Jing Tao, Hong-Yu Wang, Qiao-Li Chen, Hua Wang, Hong Zhou, Yi-Ning Yang, Shuai Chen, Liang Chen

{"title":"Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.","authors":"Min Xu, Zi-Yue Chen, Yang Li, Yue Li, Ge Guo, Rong-Zheng Dai, Na Ni, Jing Tao, Hong-Yu Wang, Qiao-Li Chen, Hua Wang, Hong Zhou, Yi-Ning Yang, Shuai Chen, Liang Chen","doi":"10.1038/s44318-024-00288-x","DOIUrl":"https://doi.org/10.1038/s44318-024-00288-x","url":null,"abstract":"Lipid droplets (LDs) serve as crucial hubs for lipid trafficking and metabolic regulation through their numerous interactions with various organelles. While the interplay between LDs and the Golgi apparatus has been recognized, their roles and underlying mechanisms remain poorly understood. Here, we reveal the role of Ras-related protein Rab-2A (Rab2A) in mediating LD-Golgi interactions, thereby contributing to very-low-density lipoprotein (VLDL) lipidation and secretion in hepatocytes. Mechanistically, our findings identify a selective interaction between Golgi-localized Rab2A and 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) protein residing on LDs. This complex facilitates dynamic organelle communication between the Golgi apparatus and LDs, thus contributing to lipid transfer from LDs to the Golgi apparatus for VLDL2 lipidation and secretion. Attenuation of Rab2A activity via AMP-activated protein kinase (AMPK) suppresses the Rab2A-HSD17B13 complex formation, impairing LD-Golgi interactions and subsequent VLDL secretion. Furthermore, genetic inhibition of Rab2A and HSD17B13 in the liver reduces the serum triglyceride and cholesterol levels. Collectively, this study provides a new perspective on the interactions between the Golgi apparatus and LDs.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577097","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

TRPC5: a new entry to the chromaffin cell's palette of ion channels that control adrenal response to hypoglycemia. TRPC5：控制肾上腺对低血糖反应的绒毛膜细胞离子通道的新成员。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 DOI: 10.1038/s44318-024-00286-z

Emilio Carbone

引用次数: 0

Bridging structural biology and clinical research through in-tissue cryo-electron tomography. 通过组织内低温电子断层扫描技术架起结构生物学与临床研究之间的桥梁。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44318-024-00216-z

Kathryn Kixmoeller, Benjamin C Creekmore, Edward B Lee, Yi-Wei Chang

引用次数: 0

Unlocking metabolic insights with mouse genetic diversity. 用小鼠基因多样性揭示新陈代谢的奥秘

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44318-024-00221-2

Stewart W C Masson, Harry B Cutler, David E James

引用次数: 0

RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation. RNA 可微调雌激素受体-α 与低亲和性 DNA 基团的结合，从而实现转录调控。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44318-024-00225-y

Deepanshu Soota, Bharath Saravanan, Rajat Mann, Tripti Kharbanda, Dimple Notani

{"title":"RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.","authors":"Deepanshu Soota, Bharath Saravanan, Rajat Mann, Tripti Kharbanda, Dimple Notani","doi":"10.1038/s44318-024-00225-y","DOIUrl":"10.1038/s44318-024-00225-y","url":null,"abstract":"Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300039","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

Chromatin protein complexes involved in gene repression in lamina-associated domains. 参与板层相关结构域基因抑制的染色质蛋白复合物

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1038/s44318-024-00214-1

Stefano G Manzo, Abdelghani Mazouzi, Christ Leemans, Tom van Schaik, Nadia Neyazi, Marjon S van Ruiten, Benjamin D Rowland, Thijn R Brummelkamp, Bas van Steensel

{"title":"Chromatin protein complexes involved in gene repression in lamina-associated domains.","authors":"Stefano G Manzo, Abdelghani Mazouzi, Christ Leemans, Tom van Schaik, Nadia Neyazi, Marjon S van Ruiten, Benjamin D Rowland, Thijn R Brummelkamp, Bas van Steensel","doi":"10.1038/s44318-024-00214-1","DOIUrl":"10.1038/s44318-024-00214-1","url":null,"abstract":"Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina (NL) and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here, we performed FACS-based whole-genome genetic screens in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few NL proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors involved in RNA polymerase pausing, suggesting that regulation of transcription elongation is a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly by rewiring heterochromatin. Our data indicate that the fundamental regulators of transcription and chromatin remodeling, rather than interaction with NL proteins, play a major role in transcription regulation within LADs.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331674","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

Combining systems and synthetic biology for in vivo enzymology. 将系统生物学与合成生物学相结合，用于体内酶学研究。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1038/s44318-024-00251-w

Sara Castaño-Cerezo, Alexandre Chamas, Hanna Kulyk, Christian Treitz, Floriant Bellvert, Andreas Tholey, Virginie Galéote, Carole Camarasa, Stéphanie Heux, Luis F Garcia-Alles, Pierre Millard, Gilles Truan

{"title":"Combining systems and synthetic biology for in vivo enzymology.","authors":"Sara Castaño-Cerezo, Alexandre Chamas, Hanna Kulyk, Christian Treitz, Floriant Bellvert, Andreas Tholey, Virginie Galéote, Carole Camarasa, Stéphanie Heux, Luis F Garcia-Alles, Pierre Millard, Gilles Truan","doi":"10.1038/s44318-024-00251-w","DOIUrl":"10.1038/s44318-024-00251-w","url":null,"abstract":"Enzymatic parameters are classically determined in vitro, under conditions that are far from those encountered in cells, casting doubt on their physiological relevance. We developed a generic approach combining tools from synthetic and systems biology to measure enzymatic parameters in vivo. In the context of a synthetic carotenoid pathway in Saccharomyces cerevisiae, we focused on a phytoene synthase and three phytoene desaturases, which are difficult to study in vitro. We designed, built, and analyzed a collection of yeast strains mimicking substantial variations in substrate concentration by strategically manipulating the expression of geranyl-geranyl pyrophosphate (GGPP) synthase. We successfully determined in vivo Michaelis-Menten parameters (KM, Vmax, and kcat) for GGPP-converting phytoene synthase from absolute metabolomics, fluxomics and proteomics data, highlighting differences between in vivo and in vitro parameters. Leveraging the versatility of the same set of strains, we then extracted enzymatic parameters for two of the three phytoene desaturases. Our approach demonstrates the feasibility of assessing enzymatic parameters directly in vivo, providing a novel perspective on the kinetic characteristics of enzymes in real cellular conditions.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331675","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

Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling-induced dietary peptide uptake via PEPT-1. 胰岛素/IGF-1 信号通过 PEPT-1 诱导的膳食肽吸收对生殖细胞蛋白稳态的非细胞自主调节

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44318-024-00234-x

Tahir Muhammad, Stacey L Edwards, Allison C Morphis, Mary V Johnson, Vitor De Oliveira, Tomasz Chamera, Siyan Liu, Ngoc Gia Tuong Nguyen, Jian Li

{"title":"Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling-induced dietary peptide uptake via PEPT-1.","authors":"Tahir Muhammad, Stacey L Edwards, Allison C Morphis, Mary V Johnson, Vitor De Oliveira, Tomasz Chamera, Siyan Liu, Ngoc Gia Tuong Nguyen, Jian Li","doi":"10.1038/s44318-024-00234-x","DOIUrl":"10.1038/s44318-024-00234-x","url":null,"abstract":"Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300037","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

Ezrin, radixin, and moesin are dispensable for macrophage migration and cellular cortex mechanics. Ezrin、radixin 和 moesin 对于巨噬细胞迁移和细胞皮层力学是不可或缺的。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-07-18 DOI: 10.1038/s44318-024-00173-7

Perrine Verdys, Javier Rey Barroso, Adeline Girel, Joseph Vermeil, Martin Bergert, Thibaut Sanchez, Arnaud Métais, Thomas Mangeat, Elisabeth Bellard, Claire Bigot, Catherine Astarie-Dequeker, Arnaud Labrousse, Jean-Philippe Girard, Isabelle Maridonneau-Parini, Christel Vérollet, Frédéric Lagarrigue, Alba Diz-Muñoz, Julien Heuvingh, Matthieu Piel, Olivia du Roure, Véronique Le Cabec, Sébastien Carréno, Renaud Poincloux

{"title":"Ezrin, radixin, and moesin are dispensable for macrophage migration and cellular cortex mechanics.","authors":"Perrine Verdys, Javier Rey Barroso, Adeline Girel, Joseph Vermeil, Martin Bergert, Thibaut Sanchez, Arnaud Métais, Thomas Mangeat, Elisabeth Bellard, Claire Bigot, Catherine Astarie-Dequeker, Arnaud Labrousse, Jean-Philippe Girard, Isabelle Maridonneau-Parini, Christel Vérollet, Frédéric Lagarrigue, Alba Diz-Muñoz, Julien Heuvingh, Matthieu Piel, Olivia du Roure, Véronique Le Cabec, Sébastien Carréno, Renaud Poincloux","doi":"10.1038/s44318-024-00173-7","DOIUrl":"10.1038/s44318-024-00173-7","url":null,"abstract":"The cellular cortex provides crucial mechanical support and plays critical roles during cell division and migration. The proteins of the ERM family, comprised of ezrin, radixin, and moesin, are central to these processes by linking the plasma membrane to the actin cytoskeleton. To investigate the contributions of the ERM proteins to leukocyte migration, we generated single and triple ERM knockout macrophages. Surprisingly, we found that even in the absence of ERM proteins, macrophages still form the different actin structures promoting cell migration, such as filopodia, lamellipodia, podosomes, and ruffles. Furthermore, we discovered that, unlike every other cell type previously investigated, the single or triple knockout of ERM proteins does not affect macrophage migration in diverse contexts. Finally, we demonstrated that the loss of ERMs in macrophages does not affect the mechanical properties of their cortex. These findings challenge the notion that ERMs are universally essential for cortex mechanics and cell migration and support the notion that the macrophage cortex may have diverged from that of other cells to allow for their uniquely adaptive cortical plasticity.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724971","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

IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat. IF1 是 ATP 合成酶水解活性的冷调节开关，支持棕色脂肪的热生成。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44318-024-00215-0

Henver S Brunetta, Anna S Jung, Fernando Valdivieso-Rivera, Stepheny C de Campos Zani, Joel Guerra, Vanessa O Furino, Annelise Francisco, Marcelo Berçot, Pedro M Moraes-Vieira, Susanne Keipert, Martin Jastroch, Laurent O Martinez, Carlos H Sponton, Roger F Castilho, Marcelo A Mori, Alexander Bartelt

{"title":"IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.","authors":"Henver S Brunetta, Anna S Jung, Fernando Valdivieso-Rivera, Stepheny C de Campos Zani, Joel Guerra, Vanessa O Furino, Annelise Francisco, Marcelo Berçot, Pedro M Moraes-Vieira, Susanne Keipert, Martin Jastroch, Laurent O Martinez, Carlos H Sponton, Roger F Castilho, Marcelo A Mori, Alexander Bartelt","doi":"10.1038/s44318-024-00215-0","DOIUrl":"10.1038/s44318-024-00215-0","url":null,"abstract":"While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called \"reverse mode\" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300035","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