The FEBS journal最新文献

{"title":"Neocortical neurogenesis: a proneural gene perspective.","authors":"Lakshmy Vasan, Alexandra Moffat, Pierre Mattar, Carol Schuurmans","doi":"10.1111/febs.70158","DOIUrl":"10.1111/febs.70158","url":null,"abstract":"<p><p>The neocortex, which is the site of higher-order cognitive functioning, is comprised of two main neuronal types: excitatory (E) and inhibitory (I). Neurodevelopmental disorders that disrupt the balance of E:I neurotransmission predispose individuals to atypical brain function, highlighting the importance of generating the correct numbers of each neuronal type. During development, neurons with E and I neurotransmission profiles are primarily generated from neural stem and progenitor cells (NPCs), located in the dorsal and ventral telencephalon, respectively. To ensure that correct numbers of each neuronal type are generated, NPC differentiation dynamics vary depending on positional and temporal information and host species. Despite variations in NPC differentiation kinetics and outcomes, proneural genes encoding basic helix-loop-helix (bHLH) transcription factors (TFs) have remained constant as the core drivers of neurogenesis and neuronal subtype specification from fly to human. This high degree of functional conservation raises the question of how proneural TF activity is regulated to control precise neurogenic patterns. In the neocortex, the proneural genes neurogenin 1 (Neurog1) and Neurog2 specify an excitatory neuronal identity in dorsal telencephalic NPCs, whereas achaete-scute family bHLH transcription factor 1 (Ascl1) specifies an inhibitory neurotransmission fate in ventral NPCs, generating interneurons that then migrate tangentially to enter the neocortex. Here, we review our current knowledge of how Neurog1/Neurog2 and Ascl1 functions are regulated to ensure that E:I balance is ultimately achieved in the lissencephalic murine cortex and in gyrencephalic species. Together, these studies point to emergent and conserved features of proneural gene regulation and function across evolutionary time.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370023","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}

{"title":"Short coiled-coil proteins from plants and metazoans - the 'jacks of all trades'.","authors":"Agnieszka Sirko, Jarosław Poznański, Marzena Sieńko","doi":"10.1111/febs.70159","DOIUrl":"10.1111/febs.70159","url":null,"abstract":"<p><p>The molecular functions of short coiled-coil proteins remain poorly characterized. These proteins typically act as facilitators rather than essential components of metabolic processes, contributing to cellular homeostasis, and are aptly described as 'jacks of all trades but masters of none'. They are found across diverse groups of organisms, including both plants and animals. LSU (RESPONSE TO LOW SULFUR) are plant proteins induced under sulfur deficiency and other environmental stresses. They participate in metabolic pathways, including sulfate assimilation, and manage oxidative stress by stabilizing and protecting antioxidative enzymes. In metazoans, SCOC (SHORT COILED-COIL) proteins regulate autophagy initiation by recruiting proteins essential for forming autophagosomes-key vesicles involved in cellular degradation. SCOC proteins also interact with factors critical for maintaining membrane dynamics and intracellular transport. Despite some functional similarities, the roles of these proteins have diverged significantly between plants and animals, reflecting organism-specific adaptations shaped by evolutionary pressures. This divergence underscores their adaptive versatility and highlights their potential as promising targets for future biological research.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370024","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}

{"title":"Research highlights","authors":"Julija Hmeljak","doi":"10.1111/febs.70152","DOIUrl":"https://doi.org/10.1111/febs.70152","url":null,"abstract":"<p>In this issue, we highlight four new research papers that span the breadth of <i>The FEBS Journal</i>'s scope and demonstrate that the molecular life sciences field remains as vibrant as ever. Within their diversity, all four papers carry a metabolism component: Giannoni <i>et al</i>. provide a translationally relevant link between cancer cell metabolism and sex-determined immune responses in melanoma. Logan and team solve the structure of a bacterial transcriptional repressor that functions as a flexible nucleotide sensor. Kappel and colleagues probe signalling pathways in soil fungi, providing important insights into the dynamics of soil communities. Finally, Bortoluci's group describes a glycolysis-linked caspase-11-dependent mechanism that suppresses Zika virus replication in astrocytes.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 12","pages":"3034-3036"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315004","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}

{"title":"Alternative substrate-assisted hydrolysis pathways of posttransfer editing by prokaryotic leucyl-tRNA synthetase.","authors":"Mykola M Ilchenko, Alexey Rayevsky, Oksana P Kovalenko, Evgeny Demianenko, Oleksandra I Skydanovych, Igor Ya Dubey, Michael A Tukalo","doi":"10.1111/febs.70153","DOIUrl":"https://doi.org/10.1111/febs.70153","url":null,"abstract":"<p><p>Leucyl-tRNA synthetase (LeuRS) activates cognate leucine and wrongly activates norvaline (and other proteinogenic and non-proteinogenic amino acids), but then mischarges tRNA. Here, we studied the editing mechanisms of Thermus thermophilus LeuRS (TthLeuRS) by combination of biochemical and computational investigations with the appropriate substrate, norvalyl-tRNA, as previously reported for E. coli LeuRS (EcLeuRS). Based on DFT (density functional theory) calculations, we have proposed three alternative hydrolysis mechanisms. These mechanisms differ according to which group of water molecules present in the editing site of the enzyme-substrate complex participates in the chemical reaction of ester bond cleavage. The main feature of the proposed deacylation pathways is direct assistance by the substrate in the hydrolysis process. In all three cases, the 3'-OH group of the substrate directly participates in the reaction. To confirm the proposed models, the experimental substitution of the 76 3'-OH group of the tRNA^Leu was constructed yielding a tRNA that is devoid of editing activity. QM and metadynamics have shown that hydrolysis occurs via a common underlying catalysis mechanism involving more than one water molecule. An important element of hydrolysis is the involvement of several amino acid residues of the active centre of enzymatic editing (Asp-347/Asp-344 and Thr-247) in the process of catalytic deacylation. In conclusion, it was noted that the possibility of several alternative hydrolysis pathways may indicate that a sufficiently protected and flexible error-editing mechanism has been implemented for prokaryotic leucyl-tRNA synthetase.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304201","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}

{"title":"Epithelial cell shape changes contribute to regulation of ureteric bud branching morphogenesis.","authors":"Kristen Kurtzeborn, Vladislav Iaroshenko, Tomáš Zárybnický, Julia Koivula, Heidi Anttonen, Otto J M Mäkelä, Darren Bridgewater, Ramaswamy Krishnan, Ping Chen, Satu Kuure","doi":"10.1111/febs.70156","DOIUrl":"https://doi.org/10.1111/febs.70156","url":null,"abstract":"<p><p>Branching morphogenesis orchestrates organogenesis in many tissues, including the kidney, where ureteric bud (UB) branching determines kidney size and shape and the final nephron number. Molecular regulation of UB branching is rather well studied, whereas the cellular mechanisms and tissue organization during UB arborization are less understood. Here, we characterized epithelial cell morphology in three dimensions (3D), studied mechanisms regulating cell shape changes, and analyzed their contribution to novel branch initiation in normal and branching-incompetent bud tips. Unbiased machine-learning-based segmentation of tip epithelia identified geometrical round-to-elliptical transformation as a key cellular mechanism facilitating growth direction changes to gain optimal branching complexity. Cell shape and molecular analyses in branching-incompetent epithelia demonstrated a distinct failure to condense cell size and modify its conformation. This, together with changes in adhesive forces, defective actin dynamics, and disorganization in myosin-9 (MYH9)-based microtubules, suggests altered biophysical properties in tip cells, where branch point decisions are made and actualized. The data demonstrate that dynamic changes in volume and morphology of individual epithelial cells, together with optimal traction stress, facilitate novel branch formation in the UB tip niche. Based on these results, we propose a model where epithelial cell crowding, in tandem with stretching, transforms individual cells into elliptical and elongated shapes. This creates local curvatures that drive new branch formation during the ampulla-to-asymmetric ampulla transition of the UB.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304202","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}

{"title":"The toxic effects of meta-tyrosine are related to its misincorporation into the proteome and to altered metabolism in cyanobacteria.","authors":"Hagit Zer, Roei Matan, David Rasin, Yoram Soroka, Noa Carmi, Hanan Schoffman, Nir Keren, Jörg Nickelsen, Oren Ostersetzer-Biran","doi":"10.1111/febs.70154","DOIUrl":"https://doi.org/10.1111/febs.70154","url":null,"abstract":"<p><p>Cyanobacteria are prolific photosynthetic bacteria whose notable adaptability, coupled with a high metabolic versatility, enables them to thrive in diverse habitats across the globe. They play a key role in global primary production and nutrient cycling, but uncontrolled proliferation of certain species can harm aquatic life. Cyanobacterial blooms (cyanoblooms), triggered by factors such as nutrient influx, temperature, and light, significantly impact ecosystem dynamics and are intensifying due to global warming. Currently, there are no efficient means to mitigate these effects. Here, we show that meta-tyrosine (m-Tyr), a nonproteinogenic amino acid analog of aromatic amino acids (e.g., Phe and Tyr), is highly toxic to various cyanobacteria, whereas non-photosynthetic bacteria appear to be much less susceptible to m-Tyr. Examination of the molecular basis of m-Tyr toxicity in the model organism Synechocystis sp. PCC6803 is complex. Molecular and biochemical analyses indicate altered amino acid homeostasis in m-Tyr-treated cyanobacteria. Proteomic studies further showed that m-Tyr is misincorporated by phenylalanyl-tRNA synthetase (PheRS) into the Synechocystis proteome, particularly affecting ribosomal as well as photosynthetic-related proteins. Likewise, m-Tyr-treated Synechocystis exhibit altered translational and photosynthetic activities, which are tightly correlated with growth retardation and morphological changes at micromolar m-Tyr concentrations, and increased mortality at higher concentrations. These findings indicate that the toxicity of m-Tyr to Synechocystis results from a combination of cellular effects, including altered metabolism and its incorporation into the cyanobacterial proteome. This understanding might also contribute to the development of novel natural compounds for controlling harmful cyanoblooms.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304203","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}

{"title":"Ultraviolet radiation induces caspase cleavage and nuclear translocation of heme oxygenase 1 (HO-1) to activate autophagy in skin keratinocytes.","authors":"Chunxiang Bian, Yan Wu, Mingwang Zhang, Lan Ge, Maojiao Zhong, Chunling Zheng, Long Chen, Mingxing Lei, Muhammad Farrukh Nisar, Charareh Pourzand, Jörg W Bartsch, Julia Li Zhong, Mei Wang","doi":"10.1111/febs.70144","DOIUrl":"https://doi.org/10.1111/febs.70144","url":null,"abstract":"<p><p>The skin is vulnerable to ultraviolet (UV) exposure, and as a repair mechanism, autophagy activation is essential to eliminate UV-damaged skin cells to maintain tissue homeostasis. As a UV-induced protein, heme oxygenase-1 (HO-1; 32 kDa) is implicated in protecting cells from oxidative stress and plays an important role in disease prevention. However, the mechanism of photoprotection in skin cells has yet to be fully understood. In the current study, we uncovered that UV radiation induces proteolytic cleavage of HO-1 into a 26 kDa product that accumulates in the cell nucleus. Biochemical analyses show that caspase-1 (CASP1) directly binds to HO-1 and cleaves full-length HO-1 at the C terminus. It is further unveiled that the 26 kDa HO-1 product is a stronger activator of autophagy than full-length HO-1, as demonstrated by the activation of autophagy-related genes. Moreover, the 26 kDa HO-1 cleavage product promotes translocation of the transcription factor basic helix-loop-helix ARNT-like protein 1 (Bmal1) into the cell nucleus. This translocation appears to be required for the induction of autophagy, as knocking down Bmal1 fails to activate autophagy induced by the 26 kDa HO-1 cleavage product. We conclude that a proteolytic cascade involving CASP1/HO-1/Bmal1 acts to modulate autophagy in UV-irradiated human skin keratinocytes, presumably as a mechanism to mediate UV photoprotection. Our study identified proteolysis as a regulatory event by generating a previously unknown 26 kDa form of HO-1 to play a distinct role in the activation of autophagy in UV-exposed epidermal cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251621","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}

{"title":"Insulin facilitates entry of calcium ions into human and murine erythrocytes via Piezo1: a newly identified mechanism with implications for type 2 diabetes.","authors":"Lennart Kuck, Tia A Griffith, Antony P McNamee, Jason N Peart, John H Wilson, Ajay Sharma, Lavanya A Sharma, Kai Robertson, Eugene F Du Toit, Michael J Simmonds","doi":"10.1111/febs.70157","DOIUrl":"https://doi.org/10.1111/febs.70157","url":null,"abstract":"<p><p>Circulatory deficits are common and pathophysiologically relevant in type 2 diabetes mellitus (T2DM). Perturbed red blood cell (RBC) homeostasis and diminished nitric oxide (NO) availability contribute to endothelial dysfunction, a hallmark of cardiometabolic disorders; however, underlying pathophysiological mechanisms remain elusive. Here, we investigated RBC signaling pathways in a murine model of metabolic disease, focused on NO. T2DM-RBCs had elevated levels of cytosolic NO, intracellular calcium ions (Ca²⁺), and reactive oxygen species. Acute stimulation with exogenous insulin had no effect on NO content. Whereas insulin exposure caused Ca²⁺ entry into healthy RBCs, T2DM-RBCs were insensitive. Using RBCs isolated from human blood, we confirmed that insulin had no effect on RBC-NO, despite prompting Ca²⁺ uptake. Ca²⁺ uptake with insulin exposure was sensitive to inhibition of mechanosensitive ion channels, as well as Ca²⁺ chelation. Furthermore, co-incubation of RBCs with the piezo-type mechanosensitive ion channel component 1 (Piezo1) channel agonist Yoda1 and insulin did not produce compounded Ca²⁺ uptake, raising the possibility of crosstalk between insulin and Piezo1. The hyperinsulinemia associated with T2DM may exacerbate normal Piezo1-dependent Ca²⁺ uptake into RBCs, contributing to RBC dysfunction and circulatory complications in T2DM. The significance of RBC signaling in the pathophysiology of cardiometabolic disorders is still emerging. Individuals carrying mutations in the PIEZO1 gene exhibit hematological aberrations and hereditary anemia, supporting the importance of Piezo1 in RBC homeostasis. Furthermore, a shift in RBC-NO metabolism favoring nitrosative stress may contribute to circulatory complications observed in metabolic diseases such as T2DM. Collectively, the emerging relevance of RBC signaling pathways may provide novel avenues for targeted drug development.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251620","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}

{"title":"Biochemical and structural characterization of chlorite dismutase enzyme from Pseudomonas aeruginosa.","authors":"Dimitrios V Nokas, Eleni K Panagiotopoulou, Antonios I Kapogiannatos, Georgios E Premetis, Nikolaos E Labrou, Eleni K Efthimiadou, Anastassios C Papageorgiou, Evangelia G Chronopoulou","doi":"10.1111/febs.70151","DOIUrl":"https://doi.org/10.1111/febs.70151","url":null,"abstract":"<p><p>Industrialization and urbanization have caused serious contamination of water bodies, and the removal of chemical contaminants has become a major challenge. Chlorite is a harmful anthropogenic compound with a serious environmental impact and has been detected in groundwater, drinking water, and soil. Enzymes are considered sustainable tools for bioremediation, with chlorite dismutase (Cld) being a notable example. This enzyme has unique properties owing to the rare dioxygen bond formation that it catalyzes. In the present study, we report the cloning, biochemical, and structural characterization of the dimeric Cld from Pseudomonas aeruginosa (PaCld). PaCld is a heme b oxidoreductase that can decompose chlorite ( <math> <semantics> <mrow><msubsup><mi>ClO</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{ClO}}_2^{-} $$</annotation></semantics> </math> or OClO^-) into harmless chloride (Cl^-) and dioxygen (O₂) with high turnover rates. The structure of PaCld was determined at atomic (0.99 Å) resolution using X-ray crystallography. Additionally, steady-state kinetics and stability studies provided valuable insights into the catalytic mechanism of dimeric Clds. Apart from chlorite bioremediation of water, Clds can also be used in biomedical and synthetic biology as well as in enzymatic cascades with O₂-utilizing enzymes.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210610","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}

{"title":"A guide to heat shock factors as multifunctional transcriptional regulators.","authors":"Hendrik S E Hästbacka, Alejandro J Da Silva, Lea Sistonen, Eva Henriksson","doi":"10.1111/febs.70139","DOIUrl":"https://doi.org/10.1111/febs.70139","url":null,"abstract":"<p><p>The heat shock factors (HSFs) form a family of transcription factors, which are evolutionarily conserved in eukaryotes. They are best known as transcriptional regulators of molecular chaperone genes, including those encoding heat shock proteins, in response to heat shock and other protein-damaging stresses. Since the discovery of the first HSF and its eponymous role in the heat shock response four decades ago, the currently known HSFs in vertebrates, that is, HSF1-5, HSFX, and HSFY, have been implicated in a wide array of physiological and pathological processes, including organismal development and cancer progression. To date, most studies have focused on individual HSFs, but it is becoming increasingly evident that the role of multiple HSFs and their potential crosstalk should be considered. In this review, we provide a comprehensive overview of the structures, functions, and regulation of the mammalian HSF family members and explore their interplay in biological processes. We highlight recent advancements regarding the roles of HSF family members in viral infection, cell adhesion, and spermatogenesis, and discuss the key questions to be addressed by forthcoming studies in HSF biology.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210609","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}