The FEBS journal最新文献

{"title":"Kinesin-like protein KIF18A is required for faithful coordination of chromosome congression with cytokinesis.","authors":"Su Hyun Lee, Mi-Sun Kwon, Taerim Lee, Sungchul Hohng, Hyunsook Lee","doi":"10.1111/febs.70019","DOIUrl":"https://doi.org/10.1111/febs.70019","url":null,"abstract":"<p><p>The maintenance of genetic integrity in proliferating cells requires the coordinated regulation of DNA replication, chromosome segregation, and cytokinetic abscission. Chromosome-microtubule interactions regulate mitosis, while interactions between the actin cytoskeleton and Myosin IIA dictate cytokinetic abscission. This process, crucial for the equal distribution of the duplicated genome into two daughter cells, occurs perpendicular to the axis of chromosome segregation. However, the mechanism of how microtubule-driven mitosis and actin-associated cytokinesis are precisely coordinated remains poorly understood. This study highlights the role of KIF18A, a kinesin-like protein, in linking kinetochore-microtubule dynamics to cytokinetic axis formation. KIF18A's localization changes through the cell division cycle, from the metaphase plate during chromosome congression to the central spindle in late anaphase, and finally to the spindle midbody in telophase. KIF18A depletion leads to chromosome congression failures and anaphase onset delays. Notably, cells attempting to undergo division in the absence of KIF18A exhibited disruptions in the parallel structure of the central spindle, causing mislocalization of the centralspindlin complex, such as kinesin-like protein KIF23 (also known as MKLP1) and Rac GTPase-activating protein 1 (RACGAP1). These disruptions impair cleavage furrow establishment, causing incomplete cytokinesis and the formation of mononuclear or binucleated cells. Our findings suggest that KIF18A is crucial for coordinating chromosome congression and cytokinesis by regulating the spatial and temporal assembly of the central spindle during late anaphase.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426674","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":"Cell wall-resident proteins with internal repeats (PIRs) show an inverted architecture in Neurospora crassa, but maintain their role as wall stabilizers.","authors":"Paul Montaño-Silva, Olga A Callejas-Negrete, Alejandro Pereira-Santana, Jorge Verdín","doi":"10.1111/febs.70020","DOIUrl":"https://doi.org/10.1111/febs.70020","url":null,"abstract":"<p><p>Proteins with internal repeats (PIRs) are the second most abundant class of fungal cell wall resident proteins. In yeasts, PIRs preserve the stability of the cell wall under stressful conditions. They are characterized by conserved N-terminal amino acid sequences repeated in tandem (PIR motifs), and a cysteine (Cys)-rich C-terminal domain. PIRs have been identified in several filamentous fungi genomes; however, they have not been studied beyond yeasts. In this work, the diversity, evolution, and biological role of PIRs, with a particular focus on a new PIRs class, was addressed. Bioinformatic inference of PIRs in fungi indicated they were an innovation in Ascomycota. Predicted PIRs clustered in two main groups: classical yeasts PIRs (N-terminal PIR motifs; C-terminal Cys-rich domain), and PIRs from filamentous fungi with an inverted architecture (N-terminal Cys-rich domain; C-terminal PIR motifs), which could harbor additional glycosylphosphatidylinositol (GPI) addition-signals. As representatives of the second group, Neurospora crassa (Nc) PIR-1 (NCU04033) and PIR-2 (NCU07569) were studied. Confocal microscopy of eGFP-labeled Nc PIR-1 and Nc PIR-2 revealed they accumulate in apical plugs; additionally, PIR-1 requires the Kex2 processing site for correct maturation and harbors a predicted GPI modification signal. Moreover, Nc Δpir-1 and Δpir-2 single mutants showed a growth rate similar to that of Nc wild-type (WT), but the double mutant Nc Δpir-1/Δpir-2 grew significantly slower. Similarly, Nc Δpir-1 and Nc Δpir-2 were mildly sensitive to calcofluor white, although Nc Δpir-1/Δpir-2 double mutant was severely impaired. Despite the inverted architecture of Nc PIR-1 and Nc PIR-2, they maintain a role as cell wall stabilizers like classical yeast PIRs.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416604","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":"Quantitative proteomics identifies possible flow of metastatic cues between progressive stages of colorectal cancer via transfer of ceramide-dependent exosomal cargoes.","authors":"Dipanjana Ghosh, Teck Kwang Lim, Anindya Basu, Julia Christina Gross, Qingsong Lin","doi":"10.1111/febs.17410","DOIUrl":"https://doi.org/10.1111/febs.17410","url":null,"abstract":"<p><p>Cancer metastasis is largely influenced by cell-cell communication, to which exosomes play a vital role. Exosomes are small extracellular vesicles (sEVs) that originate as intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) during endosome maturation. ILV formation depends on several pathways, including that of ceramide synthesis by neutral sphingomyelinase 2 [nSMase2]. Colorectal cancer (CRC)-derived sEVs are reported to carry a diverse range of metastatic cargo proteins; however, segregation of them in the ceramide-dependent sEV pool (sEV^Cer) remains unexplored. The current study aimed to identify the metastatic proteins that are secreted through sEV^Cer, from CRC cells of variable metastatic potentials. Primary (SW480) and metastatic (SW620) CRC cells were treated with nSMase2 blocker and sEVs were isolated, followed by extraction of the sEV proteins for a quantitative proteomic profiling using isobaric tags for relative and absolute quantitation (iTRAQ). In total, 1781 proteins were identified with unused protein score > 1.3. Of these identified proteins, 22.8% and 17.01% were found to be depleted within sEVs of the treated SW480 and SW620 cells, respectively. These depleted protein pools represented the cargo that are preferentially secreted through sEV^Cer in respective cell types (Cargo^Cer-SW480 and Cargo^Cer-SW620). Cargo^Cer-SW480 overrepresented integrin signaling pathway members and Cargo^Cer-SW620 overrepresented integrin as well as platelet-derived growth factor (PDGF) signaling pathway members. Interestingly, the uniquely overrepresented Cargo^Cer-SW480 and Cargo^Cer-SW620 were biologically connected, rendering possible transfer of metastatic cues via sEV^Cer. Overall, this study identified Cargo^Cer and their dynamics over progressive CRC stages, and thereby opens up a new research direction for exploring the flow of metastatic cues through uptake and release of sEV^Cer.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416612","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":"Functional consequences of lysine acetylation of phosphofructokinase isozymes.","authors":"Xinyu Li, Nour Fatema, Qinglei Gan, Chenguang Fan","doi":"10.1111/febs.70014","DOIUrl":"https://doi.org/10.1111/febs.70014","url":null,"abstract":"<p><p>Phosphofructokinase (Pfk) catalyzes the phosphorylation of fructose 6-phosphate and is a key regulatory point in the glycolysis pathway. Multiple lysine residues in both Pfk isozymes, PfkA and PfkB, have been identified to be acetylated in Escherichia coli by proteomic studies, but no studies have been implemented to further characterize these acetylation events. To investigate the role of Pfk acetylation, the genetic code expansion strategy was used to generate homogeneously acetylated Pfk variants at target lysine sites that have been reported to be acetylated in nature. We found that acetylation of K309 of PfkA and K27 of PfkB decreased PfK enzyme activities significantly. We further investigated the deacetylation and acetylation processes of Pfk isozymes biochemically and genetically. Acetyl phosphate-mediated non-enzymatic acetylation could be the major mechanism of Pfk isozyme acetylation in E. coli, whereas NAD-dependent protein deacylase CobB can remove most of the acetylated lysine residues but not K309 of PfkA and K27 of PfkB, which affect enzyme activities. Because of the important role of Pfk in cellular metabolism, the results of the present study are expected to facilitate studies in the fields of metabolic engineering and research.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412234","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 signal transduction blind spot: the function of adenylyl cyclase transmembrane domains.","authors":"Ryan S Dowsell, Matthew G Gold","doi":"10.1111/febs.70022","DOIUrl":"https://doi.org/10.1111/febs.70022","url":null,"abstract":"<p><p>Signal transduction of external primary signals into intracellular elevations of the second messenger cyclic AMP is an ancient and universal regulatory mechanism in biology. In mammals, 9 of the 10 adenylyl cyclases (ACs) share a common topology that includes a large transmembrane (TM) domain assembled from two clusters of six helices. This domain accounts for ~ 35% of the coding sequence but, remarkably, its function is still an open question. In this viewpoint, we consider how the first primary AC sequences spurred ideas for the purpose of AC TM domains, including voltage-sensing and transporter functions. In the original conceptions of second messenger signalling, ACs were put forward as potential receptors, and we discuss emerging evidence in support of this function. We also consider growing evidence that cyclase TM helical bundles help to organise multiprotein signalling complexes by engaging in interactions with other membrane-embedded proteins. Cyclase TM regions are more diverse between isoforms than the catalytic domain-we conclude by considering how this might be exploited in therapeutic strategies targeting specific cyclase isoforms.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412233","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":"Crystal structure of Anopheles gambiae actin depolymerizing factor explains high affinity to monomeric actin.","authors":"Devaki Lasiwa, Inari Kursula","doi":"10.1111/febs.70007","DOIUrl":"https://doi.org/10.1111/febs.70007","url":null,"abstract":"<p><p>Actin is an intrinsically dynamic protein, the function and state of which are modulated by actin-binding proteins. Actin-depolymerizing factors (ADF)/cofilins are ubiquitous actin-binding proteins that accelerate actin turnover. Malaria is an infectious disease caused by parasites of the genus Plasmodium, which belong to the phylum Apicomplexa. The parasites require two hosts to complete their life cycle: the definitive host, or the vector, an Anopheles spp. mosquito, and a vertebrate intermediate host, such as humans. Here, the malaria vector Anopheles gambiae ADF (AgADF) crystal structure is reported. AgADF has a conserved ADF/cofilin fold with six central β-strands surrounded by five α-helices with a long β-hairpin loop protruding out of the structure. The G- and F-actin-binding sites of AgADF are conserved, and the structure shows features of potential importance for regulation by membrane binding and redox state. AgADF binds monomeric ATP- and ADP-actin with a high affinity, having a nanomolar K_d, and binds effectively also to actin filaments.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392798","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":"Saccharomyces cerevisiae Dmo2p is required for the stability and maturation of newly translated Cox2p.","authors":"Maria Antônia Kfouri Martins Soares, Letícia Veloso Ribeiro Franco, Jhulia Almeida Clarck Chagas, Fernando Gomes, Mário H Barros","doi":"10.1111/febs.70009","DOIUrl":"https://doi.org/10.1111/febs.70009","url":null,"abstract":"<p><p>Based on available platforms detailing the Saccharomyces cerevisiae mitochondrial proteome and other high-throughput studies, we identified the yeast gene DMO2 as having a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homologue to human distal membrane-arm assembly complex protein 1 (DMAC1); both proteins have two conserved cysteines in a Cx₂C motif. Here, we localised Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The respiratory deficiency of dmo2 mutants at 37°C led to a reduction in cytochrome c oxidase (COX) activity (COX) and in the formation of cytochrome bc₁ complex-COX supercomplexes; dmo2 also has a rapid turnover of Cox2p, the second subunit of the COX complex that harbours the binuclear Cu_A centre. Moreover, Dmo2p co-immunoprecipitates with Cox2p and components required for maturation of the Cu_A centre, such as Sco1p and Sco2p. Finally, DMO2 overexpression can suppress cox23 respiratory deficiency, a mutant that has impaired mitochondrial copper homeostasis. Mass spectrometry data unveiled the interaction of Dmo2p with different large molecular complexes, including bc₁-COX supercomplexes, the TIM23 machinery and the ADP/ATP nucleotide translocator. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392816","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":"Redox imbalance and hypoxia-inducible factors: a multifaceted crosstalk.","authors":"Ravi, Jogender Singh","doi":"10.1111/febs.70013","DOIUrl":"https://doi.org/10.1111/febs.70013","url":null,"abstract":"<p><p>Redox homeostasis, the delicate balance between oxidative and reductive processes, is crucial for cellular function and overall organismal health. At the molecular level, cells need to maintain a fine balance between the levels of reactive oxygen species (ROS) and reducing equivalents such as glutathione and nicotinamide adenine dinucleotide phosphate. The perturbation of redox homeostasis due to excessive ROS production leads to oxidative stress that can damage lipids, proteins, and nucleic acids. Conversely, an overly reduced cellular environment due to overabundant reducing equivalents results in reductive stress, which also interferes with important cellular signaling and physiological processes. Disrupted redox homeostasis is linked to various pathological conditions, including neurodegenerative diseases, inflammatory diseases, cancer, and cardiovascular diseases. Cells employ diverse mechanisms to manage redox imbalance. The hypoxia response pathway, mediated by hypoxia-inducible factors and responsible for sensing and defending against low oxygen levels, plays a vital role in maintaining redox homeostasis. In this review, we highlight the complex and multifaceted crosstalk between hypoxia-inducible factors and redox homeostasis and discuss avenues for future research. Understanding the molecular mechanisms that link hypoxia-inducible factors to oxidative and reductive stresses is essential for comprehending several pathological conditions associated with hypoxia and redox imbalance.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392813","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":"Past, present, and future strategies for detecting and quantifying circular RNA variants.","authors":"He Lin, Vanessa M Conn, Simon J Conn","doi":"10.1111/febs.70012","DOIUrl":"https://doi.org/10.1111/febs.70012","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a family of covalently closed RNA transcripts ubiquitous across the eukaryotic kingdom. CircRNAs are generated by a class of alternative splicing called backsplicing, with the resultant circularization of a part of parental RNA producing the characteristic backsplice junction (BSJ). Because of the noncontiguous sequence of the BSJ with respect to the DNA genome, circRNAs remained hidden in plain sight through over a decade of RNA next-generation sequencing, yet over 3 million unique circRNA transcripts have been illuminated in the past decade alone. CircRNAs are expressed in a cell type-specific manner, are highly stable, with many examples of circRNAs being evolutionarily conserved and/or functional in specific contexts. However, circRNAs can be very lowly expressed and predictions of the circRNA context from BSJ-spanning reads alone can confound extrapolation of the exact sequence composition of the circRNA transcript. For these reasons, specific and ultrasensitive detection, combined with enrichment, bespoke bioinformatics pipelines and, more recently, long-read, highly processive sequencing is becoming critical for complete characterization of all circRNA variants. Concomitantly, the need for targeted detection and quantification of specific circRNAs has sparked numerous laboratory-based and commercial approaches to visualize circRNAs in cells and quantify them in biological samples, including biospecimens. This review focuses on advancements in the detection and quantification of circRNAs, with a particular focus on recent next-generation sequencing approaches to bolster detection of circRNA variants and accurately normalize between sequencing libraries.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401073","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":"Intercellular mitochondrial transfer contributes to microenvironmental redirection of cancer cell fate.","authors":"Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno","doi":"10.1111/febs.70002","DOIUrl":"https://doi.org/10.1111/febs.70002","url":null,"abstract":"<p><p>The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells in both 2D and 3D environments. Furthermore, we show mitochondrial transfer occurs between donor mammary epithelial cells and recipient cancer cells primarily through tunneling nanotubes (TNTs) with minimal amounts seen from extracellular transfer of mitochondria, likely via extracellular vesicles (EVs). This organelle exchange results in various cellular and metabolic alterations within cancer cells, reducing their proliferative potential, and making them susceptible to microenvironmental control. Our results demonstrate that mitochondrial transfer contributes to microenvironmental redirection of cancer cells through alteration of metabolic and molecular functions of the recipient cancer cells. To the best of our knowledge, this is the first description of a 3D bioprinter-assisted organoid system for studying mitochondrial transfer. These studies are also the first mechanistic insights into the process of mammary microenvironmental redirection of cancer and provide a framework for new therapeutic strategies to control cancer.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401132","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}