The FEBS journal最新文献_第7页

Gut microbiota: our fellow travellers in health & disease

The FEBS journal Pub Date : 2025-02-24 DOI: 10.1111/febs.70045

John F. Cryan

引用次数: 0

Interactions of the maternal microbiome with diet, stress, and infection influence fetal development

The FEBS journal Pub Date : 2025-02-23 DOI: 10.1111/febs.70031

Chloe H Puglisi, Minjeong Kim, Modi Aldhafeeri, Megan Lewandowski, Helen E. Vuong

{"title":"Interactions of the maternal microbiome with diet, stress, and infection influence fetal development","authors":"Chloe H Puglisi, Minjeong Kim, Modi Aldhafeeri, Megan Lewandowski, Helen E. Vuong","doi":"10.1111/febs.70031","DOIUrl":"10.1111/febs.70031","url":null,"abstract":"Humans and other animals contain multitudes of microorganisms including bacteria, fungi, and viruses, which make up a diverse microbiome. Across body sites including skin, gastrointestinal tract, and oral cavity there are distinct microbial niches that are made up of trillions of microorganisms that have co-evolved to inhabit and interact with the host. The microbiome also interacts with the changing environment. This tripartite interaction between the host, microbiome, and environment suggests microbial communities play a key role in the biological processes of the host, such as development and behaviors. Over the past two decades, emerging research continues to reveal how host and microbe interactions impact nervous system signaling and behaviors, and influence neurodevelopmental, neurological, and neurodegenerative disorders. In this review, we will describe the unique features of the maternal microbiome that exist during the perinatal period and discuss evidence for the function of the maternal microbiome in offspring development. Finally, we will discuss how the maternal environment interacts with the microbiome and nervous system development and then postulate how the maternal microbiome can modify early offspring development to have lasting influence on brain health.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 6","pages":"1437-1453"},"PeriodicalIF":0.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485213","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}

引用次数: 0

Re-evaluation of PTEN as an ADP-ribosylated tankyrase binding partner.

The FEBS journal Pub Date : 2025-02-23 DOI: 10.1111/febs.70035

Chiara Bosetti, Albert Galera-Prat, Anette Schmidt, Johan Pääkkönen, Aki Manninen, Lari Lehtiö

{"title":"Re-evaluation of PTEN as an ADP-ribosylated tankyrase binding partner.","authors":"Chiara Bosetti, Albert Galera-Prat, Anette Schmidt, Johan Pääkkönen, Aki Manninen, Lari Lehtiö","doi":"10.1111/febs.70035","DOIUrl":"https://doi.org/10.1111/febs.70035","url":null,"abstract":"Tankyrases establish an intricate network of protein interactions through their ankyrin repeat cluster domains (ARCs), which bind protein partners containing a characteristic peptide defined as a tankyrase-binding motif (TBM). Once the protein complex has been formed, the proteins bound to ARCs can either undergo ADP-ribosylation by tankyrases or stay unmodified. In the past years, this web of tankyrase-centered interactions has grown as new partners have been discovered. Since the catalytic and scaffolding functions of tankyrases are extensively studied and tankyrases are targets for inhibition for therapeutic purposes, it is fundamental to explore and validate which proteins are regulated by tankyrases. In this study, we analyzed the tumor suppressor phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN as a previously reported tankyrase binding protein and substrate. Inhibition of tankyrase could stabilize PTEN, and this has been implied as a possible therapeutic strategy for using tankyrase inhibitors in cancer. However, we reveal that the described PTEN putative TBM (pTBM) does not bind tankyrase ARCs. This result is consistent with evolutionary analysis, which indicates that pTBM originated before tankyrases, unlike other validated TBMs. We employ pull-down and ADP-ribosylation assays to demonstrate that PTEN does not form a complex with tankyrase in vitro and that PTEN is not ADP-ribosylated by tankyrase. Finally, we show that, in contrast to what was previously reported, catalytic inhibition of tankyrases does not have an impact on PTEN endogenous protein levels, excluding in this way any direct connection between PTEN and tankyrases.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485214","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}

引用次数: 0

Epigenetic control of cell identities from epiblast to gastrulation.

The FEBS journal Pub Date : 2025-02-22 DOI: 10.1111/febs.70024

Katrin M Schüle, Simone Probst

引用次数: 0

Stress exposure in the mdx mouse model of Duchenne muscular dystrophy provokes a widespread metabolic response.

The FEBS journal Pub Date : 2025-02-22 DOI: 10.1111/febs.70029

Erynn E Johnson, James M Ervasti

{"title":"Stress exposure in the mdx mouse model of Duchenne muscular dystrophy provokes a widespread metabolic response.","authors":"Erynn E Johnson, James M Ervasti","doi":"10.1111/febs.70029","DOIUrl":"10.1111/febs.70029","url":null,"abstract":"Duchenne muscular dystrophy is a severe neuromuscular wasting disease that is caused by a primary defect in dystrophin protein and involves organism-wide comorbidities such as cardiomyopathy, metabolic and mitochondrial dysfunction, and nonprogressive cognitive impairments. Physiological stress exposure in the mdx mouse model of Duchenne muscular dystrophy results in phenotypic abnormalities that include locomotor inactivity, hypotension, and increased morbidity. Severe and lethal stress susceptibility in mdx mice corresponds to metabolic dysfunction in several coordinated metabolic pathways within dystrophin-deficient skeletal muscle, as well as prolonged elevation in mdx plasma corticosterone levels that extends beyond the wild-type (WT) stress response. Here, we performed a targeted mass spectrometry-based plasma metabolomics screen focused on biological stress pathways in healthy and dystrophin-deficient mdx mice exposed to mild scruff stress. One-third of the stress-relevant metabolites interrogated displayed significant elevation or depletion in mdx plasma after scruff stress and were restored to WT levels by skeletal muscle-specific dystrophin expression. The metabolic pathways of mdx mice altered by scruff stress are associated with regulation of the hypothalamic-pituitary-adrenal axis, locomotor tone, neurocognitive function, redox metabolism, cellular bioenergetics, and protein catabolism. Our data suggest that a mild stress triggers an exaggerated, multi-system metabolic response in mdx mice.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477330","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}

引用次数: 0

Binary protein interactome mapping of the Giardia lamblia proteasome lid reveals extra proteasomal functions of GlRpn11.

The FEBS journal Pub Date : 2025-02-22 DOI: 10.1111/febs.70027

Ankita Das, Atrayee Ray, Nibedita Ray Chaudhuri, Soumyajit Mukherjee, Shubhra Ghosh Dastidar, Alok Ghosh, Sandipan Ganguly, Kuladip Jana, Srimonti Sarkar

{"title":"Binary protein interactome mapping of the Giardia lamblia proteasome lid reveals extra proteasomal functions of GlRpn11.","authors":"Ankita Das, Atrayee Ray, Nibedita Ray Chaudhuri, Soumyajit Mukherjee, Shubhra Ghosh Dastidar, Alok Ghosh, Sandipan Ganguly, Kuladip Jana, Srimonti Sarkar","doi":"10.1111/febs.70027","DOIUrl":"https://doi.org/10.1111/febs.70027","url":null,"abstract":"The assembly of the 26S proteasome, a multi-subunit complex for regulated protein turnover, proceeds via the formation of intermediates. Giardia lamblia does not encode proteasome regulatory subunit Rpn12 or proteasome complex subunit Sem1, two proteins crucial for assembling the proteasome lid. To understand how the interactions between the giardial proteasome lid subunits may have changed to compensate for their absence, we used yeast two-hybrid to generate a binary interactome map of Giardia's lid subunits. Most interactions within the Giardia lid are stronger than Saccharomyces cerevisiae lid, which may compensate for Rpn12 and Sem1 absence. A notable exception was the weaker interaction between the two non-ATPase lid subunits, GlRpn11 and GlRpn8, compared to the strong interaction between yeast orthologs Rpn11 and Rpn8. The Rpn11-Rpn8 dimer provides a platform for lid assembly. Their interaction involves the insertion of a methionine residue of Rpn11 into a hydrophobic pocket of Rpn8. Molecular modeling indicates that GlRpn8's pocket is wider, reconciling the experimental observation of its weak interaction with GlRpn11. This weaker interaction may have evolved to support proteasome-independent functions of GlRpn11, which localizes to multiple subcellular regions, including the mitosomes, where other proteasome subunits cannot be detected. Functional complementation in yeast shows that GlRpn11 can influence mitochondrial function and distribution. Together these observations show that GlRpn11 functions at the mitosome. Thus, this parasite's proteasome lid has a simpler subunit architecture than that of yeast with structural attributes to support dual functionalities for GlRpn11. Such parasite-specific proteasome features provide opportunities for controlling parasite transmission.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477326","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}

引用次数: 0

ARIES domains: functional signaling units of type I interferon responses.

The FEBS journal Pub Date : 2025-02-18 DOI: 10.1111/febs.70023

Lauren M Landau, Jonathan C Kagan

{"title":"ARIES domains: functional signaling units of type I interferon responses.","authors":"Lauren M Landau, Jonathan C Kagan","doi":"10.1111/febs.70023","DOIUrl":"https://doi.org/10.1111/febs.70023","url":null,"abstract":"The innate immune system relies on a network of signaling proteins classified by shared domains, which serve as functional units that orchestrate inflammatory and host defensive activities. Within type I interferon (IFN) responses, the stimulator of interferon genes protein (STING), mitochondrial antiviral-signaling protein (MAVS), Toll-IL-1 receptor-resistance protein domain-containing adapter-inducing interferon-β (TRIF), Toll-like receptor adapter interacting with SLC15A4 on the lysosome (TASL), insulin receptor tyrosine kinase substrate protein of 53 kDa (IRSp53), and GEM interacting protein (GMIP) utilize a conserved pLxIS motif to recruit IRF family transcription factors. Notably, the pLxIS motif functions within a larger signaling unit, which is referred to here as an Activator of Interferon Expression via a pLxIS motif (ARIES) domain. ARIES domains consist of the pLxIS motif and adjacent kinase activation motifs that together drive IFN responses. This review explores how ARIES domains promote immune responses via shared and distinct signaling mechanisms, protein localization, and regulation of metabolic shifts, underscoring their evolutionary conservation and critical role in host defense.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451302","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}

引用次数: 0

Sea anemone Cys-ladder peptide Ms13-1 induces a pain response as a positive modulator of acid-sensing ion channel 1a.

The FEBS journal Pub Date : 2025-02-18 DOI: 10.1111/febs.70032

Timur A Khasanov, Konstantin S Mineev, Aleksandr P Kalinovskii, Yuliya V Korolkova, Victor A Palikov, Yulia A Palikova, Igor A Dyachenko, Sergey A Kozlov, Yaroslav A Andreev, Dmitry I Osmakov

{"title":"Sea anemone Cys-ladder peptide Ms13-1 induces a pain response as a positive modulator of acid-sensing ion channel 1a.","authors":"Timur A Khasanov, Konstantin S Mineev, Aleksandr P Kalinovskii, Yuliya V Korolkova, Victor A Palikov, Yulia A Palikova, Igor A Dyachenko, Sergey A Kozlov, Yaroslav A Andreev, Dmitry I Osmakov","doi":"10.1111/febs.70032","DOIUrl":"https://doi.org/10.1111/febs.70032","url":null,"abstract":"Acid-sensing ion channel 1a (ASIC1a) is involved in processes associated with fear, learning, and neurodegeneration within the central nervous system. However, ASIC1a is also abundant in the peripheral nervous system, where its role is still poorly understood, largely due to the lack of selective ligands. In this study, we present the discovery of the first selective positive allosteric modulator for ASIC1a, isolated from the sea anemone Metridium senile. The active compound, a peptide named Ms13-1, features a novel type of fold named 'Cys-ladder'. Ms13-1 exhibits high affinity and selectivity for ASIC1a, enhancing channel activation in response to a broad range of acidic stimuli (pH 6.9-5.5) without altering the proton affinity for the channel. Moreover, injection of Ms13-1 into the hind paw of mice provokes robust and long-lasting pain-related behavior, which is significantly attenuated by a selective ASIC1 antagonist. The discovery of this novel selective positive allosteric modulator opens up new perspectives to investigate the role of ASIC1a in various physiological processes.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451267","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}

引用次数: 0

Estrogen synthesized in the central nervous system enhances MC4R expression and reduces food intake.

The FEBS journal Pub Date : 2025-02-18 DOI: 10.1111/febs.17426

Takanori Hayashi, Kanako Kumamoto, Tatsuya Kobayashi, Xinfeng Hou, Shizuko Nagao, Nobuhiro Harada, Shinichiro Honda, Yohei Shimono, Eiji Nishio

{"title":"Estrogen synthesized in the central nervous system enhances MC4R expression and reduces food intake.","authors":"Takanori Hayashi, Kanako Kumamoto, Tatsuya Kobayashi, Xinfeng Hou, Shizuko Nagao, Nobuhiro Harada, Shinichiro Honda, Yohei Shimono, Eiji Nishio","doi":"10.1111/febs.17426","DOIUrl":"https://doi.org/10.1111/febs.17426","url":null,"abstract":"Estrogen is synthesized throughout various tissues in the body, and its production is regulated by the rate-limiting enzyme aromatase (encoded by the Cyp19a1 gene). Notably, aromatase is also expressed in central nervous system cells, allowing for localized estrogen synthesis in regions such as the hypothalamus. Estrogens produced within these neurons are referred to as neuroestrogens. In this study, we investigated the role of neuroestrogens in the regulation of appetite through modulation of hypothalamic pathways in OVX, ArKO, and aromatase-restored mice. Estrogen suppresses appetite by influencing the expression of appetite-regulating peptides, including POMC and NPY, via MC4R. We explored the direct effects of neuroestrogens, independent from ovarian estrogen, on appetite suppression and the underlying molecular mechanisms. We monitored body weight and food intake and evaluated the expression of Cyp19a1, Mc4r, and other appetite-related genes. Our findings indicate that OVX and ArKO mice exhibited increased body weight and food consumption, which correlated with altered expression of Mc4r and Cyp19a1. Conversely, restoration of Cyp19a1 expression in a neuron specific manner significantly decreased food intake and increased Mc4r expression in the hypothalamus. Furthermore, neuroestrogens enhanced leptin responsiveness. Our results imply that neuroestrogens likely contribute to appetite regulation and may be relevant for body weight reduction.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451304","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}

引用次数: 0

Hydromethylthionine sustains truncated tau-dependent inflammation-lowering effects in mouse brain.

The FEBS journal Pub Date : 2025-02-17 DOI: 10.1111/febs.70021

Renato X Santos, Sophie H Lee, Richard Lofthouse, Valeria Melis, Lianne Robinson, Michael Leith, Eline Dreesen, Paul Armstrong, Thomas Vorley, Elizabeth A Goatman, Claire Hull, Gernot Riedel, Claude M Wischik, Charles R Harrington

{"title":"Hydromethylthionine sustains truncated tau-dependent inflammation-lowering effects in mouse brain.","authors":"Renato X Santos, Sophie H Lee, Richard Lofthouse, Valeria Melis, Lianne Robinson, Michael Leith, Eline Dreesen, Paul Armstrong, Thomas Vorley, Elizabeth A Goatman, Claire Hull, Gernot Riedel, Claude M Wischik, Charles R Harrington","doi":"10.1111/febs.70021","DOIUrl":"https://doi.org/10.1111/febs.70021","url":null,"abstract":"Tauopathies are a heterogeneous mixture of neurodegenerative disorders, including Alzheimer's disease and frontotemporal dementia (FTD), characterised by the accumulation of tau filaments in brain tissue. Tau protein aggregation is inhibited by hydromethylthionine (HMT), an effect that appeared to be prevented in clinical trials for subjects already receiving acetylcholinesterase inhibitors or memantine. Since neuroinflammatory responses are associated with tauopathies, we investigated the effect of HMT on the brain immune response and inflammatory status in line 66 (L66) mice, an FTD-like model overexpressing human tau, in the presence of memantine. We determined whether HMT (5 and 15 mg·kg-1), either singly or combined with memantine (20 mg·kg-1), would have a sustained impact on neuroinflammation following the cessation of drug administration. The levels of core tau fragments in L66+/- mice (P301S/G335D-hTau) were decreased in a dose-dependent manner 12 weeks after the last administration of HMT, an effect that was not affected by memantine. HMT lowered the levels of tumour necrosis factor alpha (TNF-α), thus favouring an environment conducive to neuronal protection and repair. HMT sustained increased microglial reactivity after its discontinuation, which may assist in the removal of tau aggregates, but co-administration with memantine prevented the HMT-sustained activation of microglia. These findings indicate that HMT has a beneficial effect in reducing neuroinflammation that accompanies a decrease in the accumulation of truncated tau species and that these benefits are not susceptible to interference by memantine. In turn, the nature of drug interference between HMT and memantine seems to be independent of tau and related to microglia reactivity.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443081","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}

引用次数: 0