EMBO Journal最新文献_第4页

De novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44318-024-00322-y

Mathieu Quinodoz, Sonja Rutz, Virginie Peter, Livia Garavelli, A Micheil Innes, Elena F Lehmann, Stephan Kellenberger, Zhong Peng, Angelica Barone, Belinda Campos-Xavier, Sheila Unger, Carlo Rivolta, Raimund Dutzler, Andrea Superti-Furga

{"title":"De novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder.","authors":"Mathieu Quinodoz, Sonja Rutz, Virginie Peter, Livia Garavelli, A Micheil Innes, Elena F Lehmann, Stephan Kellenberger, Zhong Peng, Angelica Barone, Belinda Campos-Xavier, Sheila Unger, Carlo Rivolta, Raimund Dutzler, Andrea Superti-Furga","doi":"10.1038/s44318-024-00322-y","DOIUrl":"10.1038/s44318-024-00322-y","url":null,"abstract":"Volume-regulated anion channels (VRACs) are multimeric proteins composed of different paralogs of the LRRC8 family. They are activated in response to hypotonic swelling, but little is known about their specific functions. We studied two human individuals with the same congenital syndrome affecting blood vessels, brain, eyes, and bones. The LRRC8C gene harbored de novo variants in both patients, located in a region of the gene encoding the boundary between the pore and a cytoplasmic domain, which is depleted of sequence variations in control subjects. When studied by cryo-EM, both LRRC8C mutant proteins assembled as their wild-type counterparts, but showed increased flexibility, suggesting a destabilization of subunit interactions. When co-expressed with the obligatory LRRC8A subunit, the mutants exhibited enhanced activation, resulting in channel activity even at isotonic conditions in which wild-type channels are closed. We conclude that structural perturbations of LRRC8C impair channel gating and constitute the mechanistic basis of the dominant gain-of-function effect of these pathogenic variants. The pleiotropic phenotype of this novel clinical entity associated with monoallelic LRRC8C variants indicates the fundamental roles of VRACs in different tissues and organs.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"413-436"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774560","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

Structure of the Nipah virus polymerase complex.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-30 DOI: 10.1038/s44318-024-00321-z

Esra Balıkçı, Franziska Günl, Loïc Carrique, Jeremy R Keown, Ervin Fodor, Jonathan M Grimes

{"title":"Structure of the Nipah virus polymerase complex.","authors":"Esra Balıkçı, Franziska Günl, Loïc Carrique, Jeremy R Keown, Ervin Fodor, Jonathan M Grimes","doi":"10.1038/s44318-024-00321-z","DOIUrl":"10.1038/s44318-024-00321-z","url":null,"abstract":"Nipah virus is a highly virulent zoonotic paramyxovirus causing severe respiratory and neurological disease. Despite its lethality, there is no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the polymerase (L) and phosphoprotein (P), replicates and transcribes the viral RNA genome. Here, we describe structures of the Nipah virus L-P polymerase complex and the L-protein's Connecting Domain (CD). The cryo-electron microscopy L-P complex structure reveals the organization of the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L-protein, and shows how the P-protein, which forms a tetramer, interacts with the RdRp-domain of the L-protein. The crystal structure of the CD-domain alone reveals binding of three Mg ions. Modelling of this domain onto an AlphaFold 3 model of an RNA-L-P complex suggests a catalytic role for one Mg ion in mRNA capping. These findings offer insights into the structural details of the L-P polymerase complex and the molecular interactions between L-protein and P-protein, shedding light on the mechanisms of the replication machinery. This work will underpin efforts to develop antiviral drugs that target the polymerase complex of Nipah virus.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"563-586"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910752","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

The transcription factor Dof3.6/OBP3 regulates iron homeostasis in Arabidopsis. 转录因子Dof3.6/OBP3调节拟南芥的铁稳态。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 10.1038/s44318-024-00304-0

Peipei Xu, Yilin Yang, Zhongtian Zhao, Jinbo Hu, Junyan Xie, Lihua Wang, Huiqiong Zheng, Weiming Cai

{"title":"The transcription factor Dof3.6/OBP3 regulates iron homeostasis in Arabidopsis.","authors":"Peipei Xu, Yilin Yang, Zhongtian Zhao, Jinbo Hu, Junyan Xie, Lihua Wang, Huiqiong Zheng, Weiming Cai","doi":"10.1038/s44318-024-00304-0","DOIUrl":"10.1038/s44318-024-00304-0","url":null,"abstract":"Iron is an essential element for plants. Iron uptake by plants is highly regulated, but the underlying mechanism is poorly understood. Using a truncated fragment of the iron deficiency-responsive bHLH100 gene promoter, we screened the Arabidopsis transcription factor yeast one-hybrid (Y1H) library and identified the DOF family protein, OBP3, as a crucial component of the iron deficiency-signaling pathway. OBP3 is a transcriptional repressor with a C-terminal activation domain. Its expression is induced by iron deficiency. The transgenic lines that overexpress OBP3 exhibited iron overload and premature leaf necrosis, while the obp3 mutant was less tolerant of iron deficiency. It was discovered that OBP3 directly targets the Ib subgroup of bHLH gene promoters. OBP3 interacts with the bHLH transcription factor ILR3 (IAA-LEUCINE RESISTANT3), and their interaction enhances the DNA-binding ability and transcriptional promoting activity of OBP3, resulting in the positive regulation of iron deficiency-response genes. In addition, the E3 Ligase BRUTUS facilitates 26S proteasome-mediated degradation of OBP3 protein to prevent excessive iron uptake in plants. In conclusion, our research emphasizes the vital role of OBP3 in regulating plant iron homeostasis.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"251-268"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631882","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

STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NF-κB signaling. STING 可诱导 HOIP 介导的 M1 泛素链合成，从而刺激 NF-κB 信号传导。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1038/s44318-024-00291-2

Tara D Fischer, Eric N Bunker, Peng-Peng Zhu, François Le Guerroué, Mahan Hadjian, Eunice Dominguez-Martin, Francesco Scavone, Robert Cohen, Tingting Yao, Yan Wang, Achim Werner, Richard J Youle

{"title":"STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NF-κB signaling.","authors":"Tara D Fischer, Eric N Bunker, Peng-Peng Zhu, François Le Guerroué, Mahan Hadjian, Eunice Dominguez-Martin, Francesco Scavone, Robert Cohen, Tingting Yao, Yan Wang, Achim Werner, Richard J Youle","doi":"10.1038/s44318-024-00291-2","DOIUrl":"10.1038/s44318-024-00291-2","url":null,"abstract":"STING activation by cyclic dinucleotides induces IRF3- and NF-κB-mediated gene expression in mammals, as well as lipidation of LC3B at Golgi-related membranes. While mechanisms of the IRF3 response are well understood, the mechanisms of NF-κB activation via STING remain unclear. We report here that STING activation induces linear/M1-linked ubiquitin chain (M1-Ub) formation and recruitment of the LUBAC E3 ligase, HOIP, to LC3B-associated Golgi membranes where ubiquitin is also localized. Loss of HOIP prevents formation of M1-Ub chains and reduces STING-induced NF-κB and IRF3 signaling in human THP1 monocytes and mouse bone marrow-derived macrophages, without affecting STING activation. STING-induced LC3B lipidation is not required for M1-Ub chain formation or for immune-related gene expression, but the recently reported STING function in neutralizing Golgi pH may be involved. Thus, LUBAC synthesis of M1-linked ubiquitin chains mediates STING-induced innate immune signaling.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"141-165"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693734","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

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma. 分化信号通过 GRHL3 在鳞状上皮细胞和鳞状细胞癌中诱导 APOBEC3A 的表达。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-15 DOI: 10.1038/s44318-024-00298-9

Nicola J Smith, Ian Reddin, Paige Policelli, Sunwoo Oh, Nur Zainal, Emma Howes, Benjamin Jenkins, Ian Tracy, Mark Edmond, Benjamin Sharpe, Damian Amendra, Ke Zheng, Nagayasu Egawa, John Doorbar, Anjali Rao, Sangeetha Mahadevan, Michael A Carpenter, Reuben S Harris, Simak Ali, Christopher Hanley, Rémi Buisson, Emma King, Gareth J Thomas, Tim R Fenton

{"title":"Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.","authors":"Nicola J Smith, Ian Reddin, Paige Policelli, Sunwoo Oh, Nur Zainal, Emma Howes, Benjamin Jenkins, Ian Tracy, Mark Edmond, Benjamin Sharpe, Damian Amendra, Ke Zheng, Nagayasu Egawa, John Doorbar, Anjali Rao, Sangeetha Mahadevan, Michael A Carpenter, Reuben S Harris, Simak Ali, Christopher Hanley, Rémi Buisson, Emma King, Gareth J Thomas, Tim R Fenton","doi":"10.1038/s44318-024-00298-9","DOIUrl":"10.1038/s44318-024-00298-9","url":null,"abstract":"Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell-cycle stage associated with APOBEC-mediated mutagenesis. In contrast, in squamous cell carcinoma we find that, there is expansion of GRHL3expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings suggest that APOBEC3A may play a functional role during keratinocyte differentiation, and offer a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"1-29"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640206","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

FNDC1 is a myokine that promotes myogenesis and muscle regeneration. FNDC1 是一种肌动蛋白，可促进肌肉生成和肌肉再生。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 10.1038/s44318-024-00285-0

Rui Xin Zhang, Yuan Yuan Zhai, Rong Rong Ding, Jia He Huang, Xiao Chen Shi, Huan Liu, Xiao Peng Liu, Jian Feng Zhang, Jun Feng Lu, Zhe Zhang, Xiang Kai Leng, De Fu Li, Jun Ying Xiao, Bo Xia, Jiang Wei Wu

{"title":"FNDC1 is a myokine that promotes myogenesis and muscle regeneration.","authors":"Rui Xin Zhang, Yuan Yuan Zhai, Rong Rong Ding, Jia He Huang, Xiao Chen Shi, Huan Liu, Xiao Peng Liu, Jian Feng Zhang, Jun Feng Lu, Zhe Zhang, Xiang Kai Leng, De Fu Li, Jun Ying Xiao, Bo Xia, Jiang Wei Wu","doi":"10.1038/s44318-024-00285-0","DOIUrl":"10.1038/s44318-024-00285-0","url":null,"abstract":"Myogenesis is essential for skeletal muscle formation and regeneration after injury, yet its regulators are largely unknown. Here we identified fibronectin type III domain containing 1 (FNDC1) as a previously uncharacterized myokine. In vitro studies showed that knockdown of Fndc1 in myoblasts reduces myotube formation, while overexpression of Fndc1 promotes myogenic differentiation. We further generated recombinant truncated mouse FNDC1 (mFNDC1), which retains reliable activity in promoting myoblast differentiation in vitro. Gain- and loss-of-function studies collectively showed that FNDC1 promotes cardiotoxin (CTX)-induced muscle regeneration in adult mice. Furthermore, recombinant FNDC1 treatment ameliorated pathological muscle phenotypes in the mdx mouse model of Duchenne muscular dystrophy. Mechanistically, FNDC1 bound to the integrin α5β1 and activated the downstream FAK/PI3K/AKT/mTOR pathway to promote myogenic differentiation. Pharmacological inhibition of integrin α5β1 or of the downstream FAK/PI3K/AKT/mTOR pathway abolished the pro-myogenic effect of FNDC1. Collectively, these results suggested that myokine FNDC1 might be used as a therapeutic agent to regulate myogenic differentiation and muscle regeneration for the treatment of acute and chronic muscle disease.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"30-53"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683430","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

Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1038/s44318-024-00318-8

Pei-Ching Huang, Soogil Hong, Hasan F Alnaser, Eleni P Mimitou, Keun P Kim, Hajime Murakami, Scott Keeney

{"title":"Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30.","authors":"Pei-Ching Huang, Soogil Hong, Hasan F Alnaser, Eleni P Mimitou, Keun P Kim, Hajime Murakami, Scott Keeney","doi":"10.1038/s44318-024-00318-8","DOIUrl":"10.1038/s44318-024-00318-8","url":null,"abstract":"DNA double-strand breaks (DSBs) are nucleolytically processed to generate single-stranded DNA for homologous recombination. In Saccharomyces cerevisiae meiosis, this resection involves nicking by the Mre11-Rad50-Xrs2 complex (MRX), then exonucleolytic digestion by Exo1. Chromatin remodeling at meiotic DSBs is thought necessary for resection, but the remodeling enzyme was unknown. Here we show that the SWI/SNF-like ATPase Fun30 plays a major, nonredundant role in meiotic resection. A fun30 mutation shortened resection tracts almost as severely as an exo1-nd (nuclease-dead) mutation, and resection was further shortened in a fun30 exo1-nd double mutant. Fun30 associates with chromatin in response to DSBs, and the constitutive positioning of nucleosomes governs resection endpoint locations in the absence of Fun30. We infer that Fun30 promotes both the MRX- and Exo1-dependent steps in resection, possibly by removing nucleosomes from broken chromatids. Moreover, the extremely short resection in fun30 exo1-nd double mutants is accompanied by compromised interhomolog recombination bias, leading to defects in recombination and chromosome segregation. Thus, this study also provides insight about the minimal resection lengths needed for robust recombination.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"200-224"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755885","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

Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1038/s44318-024-00307-x

Daniel Ten Martin, Nicolas Jardin, Juliette Vougny, François Giudicelli, Laïla Gasmi, Naomi Berbée, Véronique Henriot, Laura Lebrun, Cécile Haumaître, Matthias Kneussel, Xavier Nicol, Carsten Janke, Maria M Magiera, Jamilé Hazan, Coralie Fassier

{"title":"Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes.","authors":"Daniel Ten Martin, Nicolas Jardin, Juliette Vougny, François Giudicelli, Laïla Gasmi, Naomi Berbée, Véronique Henriot, Laura Lebrun, Cécile Haumaître, Matthias Kneussel, Xavier Nicol, Carsten Janke, Maria M Magiera, Jamilé Hazan, Coralie Fassier","doi":"10.1038/s44318-024-00307-x","DOIUrl":"10.1038/s44318-024-00307-x","url":null,"abstract":"The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule-severing enzymes, has emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins. However, whether and how tubulin posttranslational modifications may contribute to neuronal connectivity has not yet been addressed. Here we show that the microtubule-severing proteins p60-katanin and spastin play specific roles in axon guidance during zebrafish embryogenesis and identify a key role for tubulin polyglutamylation in their functional specificity. Furthermore, our work reveals that polyglutamylases with undistinguishable activities in vitro, TTLL6 and TTLL11, play exclusive roles in motor circuit wiring by selectively tuning p60-katanin- and spastin-driven motor axon guidance. We confirm the selectivity of TTLL11 towards spastin regulation in mouse cortical neurons and establish its relevance in preventing axonal degeneration triggered by spastin haploinsufficiency. Our work thus provides mechanistic insight into the control of microtubule-driven neuronal development and homeostasis and opens new avenues for developing therapeutic strategies in spastin-associated hereditary spastic paraplegia.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"107-140"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755887","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

Rhythmic astrocytic GABA production synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44318-024-00324-w

Natalie Ness, Sandra Díaz-Clavero, Marieke M B Hoekstra, Marco Brancaccio

{"title":"Rhythmic astrocytic GABA production synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus.","authors":"Natalie Ness, Sandra Díaz-Clavero, Marieke M B Hoekstra, Marco Brancaccio","doi":"10.1038/s44318-024-00324-w","DOIUrl":"10.1038/s44318-024-00324-w","url":null,"abstract":"Astrocytes of the suprachiasmatic nucleus (SCN) can regulate sleep-wake cycles in mammals. However, the nature of the information provided by astrocytes to control circadian patterns of behavior is unclear. Neuronal circadian activity across the SCN is organized into spatiotemporal waves that govern seasonal adaptations and timely engagement of behavioral outputs. Here, we show that astrocytes across the mouse SCN exhibit instead a highly uniform, pulse-like nighttime activity. We find that rhythmic astrocytic GABA production via polyamine degradation provides an inhibitory nighttime tone required for SCN circuit synchrony, thereby acting as an internal astrocyte zeitgeber (or \"astrozeit\"). We further identify synaptic GABA and astrocytic GABA as two key players underpinning coherent spatiotemporal circadian patterns of SCN neuronal activity. In describing a new mechanism by which astrocytes contribute to circadian timekeeping, our work provides a general blueprint for understanding how astrocytes encode temporal information underlying complex behaviors in mammals.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"356-381"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774570","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

Deciphering the molecular logic of WOX5 function in the root stem cell organizer. 解密WOX5在根干细胞组织器中功能的分子逻辑

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44318-024-00302-2

Ning Zhang, Pamela Bitterli, Peter Oluoch, Marita Hermann, Ernst Aichinger, Edwin P Groot, Thomas Laux

{"title":"Deciphering the molecular logic of WOX5 function in the root stem cell organizer.","authors":"Ning Zhang, Pamela Bitterli, Peter Oluoch, Marita Hermann, Ernst Aichinger, Edwin P Groot, Thomas Laux","doi":"10.1038/s44318-024-00302-2","DOIUrl":"10.1038/s44318-024-00302-2","url":null,"abstract":"Plant and animal stem cells receive signals from their surrounding cells to stay undifferentiated. In the Arabidopsis root, the quiescent center (QC) acts as a stem cell organizer, signaling to the neighboring stem cells. WOX5 is a central transcription factor regulating QC function. However, due to the scarcity of QC cells, WOX5 functions in the QC are largely unexplored at a genomic scale. Here, we unveil the transcriptional and epigenetic landscapes of the QC and the role of WOX5 within them. We find that WOX5 functions both as a transcriptional repressor and activator, affecting histone modifications and chromatin accessibility. Our data expand on known WOX5 functions, such as the regulation of differentiation, cell division, and auxin biosynthesis. We also uncover unexpected WOX5-regulated pathways involved in nitrate transport and the regulation of basal expression levels of genes associated with mature root tissues. These data suggest a role for QC cells as reserve stem cells and primed cells for prospective progenitor fates. Taken together, these findings offer insights into the role of WOX5 at the QC and provide a basis for further analyses to advance our understanding of the nature of plant stem cell organizers.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"281-303"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669666","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