Pub Date : 2024-11-22DOI: 10.1038/s44319-024-00324-1
Rachel D Van Gelder, Nandan S Gokhale, Emmanuelle Genoyer, Dylan S Omelia, Stephen K Anderson, Howard A Young, Ram Savan
Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation. In this study, we identify mRNA splicing as a positive regulator of IFNγ production. While treatment with the combination of IL-12 and IL-2 causes synergistic induction of IFNG mRNA and protein, defying transcription-translation kinetics, we observe that NK cells treated with IL-12 alone transcribe IFNG with introns intact. When NK cells are treated with both IL-2 and IL-12, IFNG transcript is spliced to form mature mRNA with a concomitant increase in IFNγ protein. We find that IL-2-mediated intron splicing occurs independently of nascent transcription but relies upon NF-κB signaling. We propose that while IL-12 transcriptionally induces IFNG mRNA, IL-2 signaling stabilizes IFNG mRNA by splicing detained introns, allowing for rapid IFNγ protein production. This study uncovers a novel role for cytokine-induced splicing in regulating IFNγ through a mechanism potentially applicable to other inflammatory mediators.
{"title":"Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production.","authors":"Rachel D Van Gelder, Nandan S Gokhale, Emmanuelle Genoyer, Dylan S Omelia, Stephen K Anderson, Howard A Young, Ram Savan","doi":"10.1038/s44319-024-00324-1","DOIUrl":"https://doi.org/10.1038/s44319-024-00324-1","url":null,"abstract":"<p><p>Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation. In this study, we identify mRNA splicing as a positive regulator of IFNγ production. While treatment with the combination of IL-12 and IL-2 causes synergistic induction of IFNG mRNA and protein, defying transcription-translation kinetics, we observe that NK cells treated with IL-12 alone transcribe IFNG with introns intact. When NK cells are treated with both IL-2 and IL-12, IFNG transcript is spliced to form mature mRNA with a concomitant increase in IFNγ protein. We find that IL-2-mediated intron splicing occurs independently of nascent transcription but relies upon NF-κB signaling. We propose that while IL-12 transcriptionally induces IFNG mRNA, IL-2 signaling stabilizes IFNG mRNA by splicing detained introns, allowing for rapid IFNγ protein production. This study uncovers a novel role for cytokine-induced splicing in regulating IFNγ through a mechanism potentially applicable to other inflammatory mediators.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1038/s44319-024-00316-1
Lehua Chen, Bernard K van der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh
Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1-/- embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/- offspring and to altered DNA hypermethylation in Tet1-/- embryos, primarily at neurodevelopmental loci. Excess FA in Tet1-/- embryos results in phospholipid metabolite loss and reduced expression of multiple membrane solute carriers, including a FA transporter gene that exhibits increased promoter DNA methylation and thereby mimics FA deficiency. Moreover, FA deficiency reveals that Tet1 haploinsufficiency can contribute to DNA hypermethylation and susceptibility to NTDs. Overall, our study suggests that epigenetic dysregulation may underlie NTD development despite FA supplementation.
众所周知,叶酸(FA)可以预防神经管畸形(NTD),但我们不知道为什么许多人类NTD病例仍然对补充叶酸难以奏效。在这里,我们研究了DNA去甲基化酶TET1如何与母体的叶酸状态相互作用来调节小鼠胚胎大脑发育。我们发现,颅脑 NTD 在非近亲繁殖的小鼠胚胎中比近亲繁殖的 Tet1-/- 胚胎具有更高的穿透性,而且不同品系的小鼠胚胎对补充足量脂肪酸都有抵抗力。富含或缺乏脂肪酸的母体饮食与野生型和Tet1+/-后代颅骨畸形发生率增加有关,也与Tet1-/-胚胎DNA超甲基化改变有关,主要是在神经发育位点。Tet1-/- 胚胎中过量的 FA 会导致磷脂代谢物的损失和多种膜溶质载体的表达减少,其中包括一种 FA 转运体基因,该基因的启动子 DNA 甲基化增加,从而模拟 FA 缺乏。此外,FA 缺乏症揭示了 Tet1 单倍体缺乏可导致 DNA 高甲基化和 NTD 易感性。总之,我们的研究表明,尽管补充了 FA,但表观遗传失调可能是 NTD 发生的基础。
{"title":"The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.","authors":"Lehua Chen, Bernard K van der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh","doi":"10.1038/s44319-024-00316-1","DOIUrl":"https://doi.org/10.1038/s44319-024-00316-1","url":null,"abstract":"<p><p>Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1<sup>-/-</sup> embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1<sup>+/-</sup> offspring and to altered DNA hypermethylation in Tet1<sup>-/-</sup> embryos, primarily at neurodevelopmental loci. Excess FA in Tet1<sup>-/-</sup> embryos results in phospholipid metabolite loss and reduced expression of multiple membrane solute carriers, including a FA transporter gene that exhibits increased promoter DNA methylation and thereby mimics FA deficiency. Moreover, FA deficiency reveals that Tet1 haploinsufficiency can contribute to DNA hypermethylation and susceptibility to NTDs. Overall, our study suggests that epigenetic dysregulation may underlie NTD development despite FA supplementation.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1038/s44319-024-00325-0
Arthur Caplan
{"title":"Soul Men and Women-what must science do to regain public trust?","authors":"Arthur Caplan","doi":"10.1038/s44319-024-00325-0","DOIUrl":"https://doi.org/10.1038/s44319-024-00325-0","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1038/s44319-024-00320-5
Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill
A defining feature of constitutive heterochromatin compartments is the heterochromatin protein-1 (HP1) family, whose members display fast internal mobility and rapid exchange with the surrounding nucleoplasm. Here, we describe a paradoxical state for the lysine methyltransferase KMT5C characterized by rapid internal diffusion but minimal nucleoplasmic exchange. This retentive behavior is conferred by sparse sequence features that constitute two modules tethered by an intrinsically disordered linker. While both modules harbor variant HP1 interaction motifs, the first comprises adjacent sequences that increase affinity using avidity. The second motif increases HP1 effective concentration to further enhance affinity in a context-dependent manner, which is evident using distinct heterochromatin recruitment strategies and heterologous linkers with defined conformational ensembles. Despite the linker sequence being highly divergent, it is under evolutionary constraint for functional length, suggesting conformational buffering can support cooperativity between modules across distant orthologs. Overall, we show that KMT5C has evolved a robust tethering strategy that uses minimal sequence determinants to harness highly dynamic HP1 proteins for retention within heterochromatin compartments.
{"title":"KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention.","authors":"Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill","doi":"10.1038/s44319-024-00320-5","DOIUrl":"https://doi.org/10.1038/s44319-024-00320-5","url":null,"abstract":"<p><p>A defining feature of constitutive heterochromatin compartments is the heterochromatin protein-1 (HP1) family, whose members display fast internal mobility and rapid exchange with the surrounding nucleoplasm. Here, we describe a paradoxical state for the lysine methyltransferase KMT5C characterized by rapid internal diffusion but minimal nucleoplasmic exchange. This retentive behavior is conferred by sparse sequence features that constitute two modules tethered by an intrinsically disordered linker. While both modules harbor variant HP1 interaction motifs, the first comprises adjacent sequences that increase affinity using avidity. The second motif increases HP1 effective concentration to further enhance affinity in a context-dependent manner, which is evident using distinct heterochromatin recruitment strategies and heterologous linkers with defined conformational ensembles. Despite the linker sequence being highly divergent, it is under evolutionary constraint for functional length, suggesting conformational buffering can support cooperativity between modules across distant orthologs. Overall, we show that KMT5C has evolved a robust tethering strategy that uses minimal sequence determinants to harness highly dynamic HP1 proteins for retention within heterochromatin compartments.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging. We then describe the molecular changes leading to global downregulation of protein synthesis with age and review recent work dissecting the mechanisms involved in gene-specific translational regulation in complementary model organisms. These mechanisms include the recognition of regulated mRNAs by trans-acting factors such as miRNA and RNA-binding proteins, the condensation of mRNAs into repressive cytoplasmic RNP granules, and the pausing of ribosomes at specific residues. Lastly, we mention future challenges of this emerging field, possible buffering functions as well as potential links with disease.
{"title":"Regulating translation in aging: from global to gene-specific mechanisms.","authors":"Mathilde Solyga, Amitabha Majumdar, Florence Besse","doi":"10.1038/s44319-024-00315-2","DOIUrl":"https://doi.org/10.1038/s44319-024-00315-2","url":null,"abstract":"<p><p>Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging. We then describe the molecular changes leading to global downregulation of protein synthesis with age and review recent work dissecting the mechanisms involved in gene-specific translational regulation in complementary model organisms. These mechanisms include the recognition of regulated mRNAs by trans-acting factors such as miRNA and RNA-binding proteins, the condensation of mRNAs into repressive cytoplasmic RNP granules, and the pausing of ribosomes at specific residues. Lastly, we mention future challenges of this emerging field, possible buffering functions as well as potential links with disease.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s44319-024-00321-4
Francisco Díaz-Castro, Eugenia Morselli, Marc Claret
The central nervous system and adipose tissue interact through complex communication. This bidirectional signaling regulates metabolic functions. The hypothalamus, a key homeostatic brain region, integrates exteroceptive and interoceptive signals to control appetite, energy expenditure, glucose, and lipid metabolism. This regulation is partly achieved via the nervous modulation of white (WAT) and brown (BAT) adipose tissue. In this review, we highlight the roles of sympathetic and parasympathetic innervation in regulating WAT and BAT activities, such as lipolysis and thermogenesis. Adipose tissue, in turn, plays a dual role as an energy reservoir and an endocrine organ, secreting hormones that influence brain function and metabolic health. In addition, this review focuses on recently uncovered communication pathways, including extracellular vesicles and neuro-mesenchymal units, which add new layers of regulation and complexity to the brain-adipose tissue interaction. Finally, we also examine the consequences of disrupted communication between the brain and adipose tissue in metabolic disorders like obesity and type-2 diabetes, emphasizing the potential for new therapeutic strategies targeting these pathways to improve metabolic health.
{"title":"Interplay between the brain and adipose tissue: a metabolic conversation.","authors":"Francisco Díaz-Castro, Eugenia Morselli, Marc Claret","doi":"10.1038/s44319-024-00321-4","DOIUrl":"10.1038/s44319-024-00321-4","url":null,"abstract":"<p><p>The central nervous system and adipose tissue interact through complex communication. This bidirectional signaling regulates metabolic functions. The hypothalamus, a key homeostatic brain region, integrates exteroceptive and interoceptive signals to control appetite, energy expenditure, glucose, and lipid metabolism. This regulation is partly achieved via the nervous modulation of white (WAT) and brown (BAT) adipose tissue. In this review, we highlight the roles of sympathetic and parasympathetic innervation in regulating WAT and BAT activities, such as lipolysis and thermogenesis. Adipose tissue, in turn, plays a dual role as an energy reservoir and an endocrine organ, secreting hormones that influence brain function and metabolic health. In addition, this review focuses on recently uncovered communication pathways, including extracellular vesicles and neuro-mesenchymal units, which add new layers of regulation and complexity to the brain-adipose tissue interaction. Finally, we also examine the consequences of disrupted communication between the brain and adipose tissue in metabolic disorders like obesity and type-2 diabetes, emphasizing the potential for new therapeutic strategies targeting these pathways to improve metabolic health.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s44319-024-00322-3
Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori
Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process. Data from PU.1-/- mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2high-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast-inflammatory cell interactions that initiate wound scarring.
{"title":"Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring.","authors":"Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori","doi":"10.1038/s44319-024-00322-3","DOIUrl":"10.1038/s44319-024-00322-3","url":null,"abstract":"<p><p>Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process. Data from PU.1<sup>-/-</sup> mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2<sup>high</sup>-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast-inflammatory cell interactions that initiate wound scarring.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium. Strikingly, this unveiled adhesion molecules and transmembrane receptors that facilitate cytokinesis completion. Among these is Dystroglycan, which connects the extracellular matrix to the cytoskeleton via Dystrophin. Live imaging revealed that Dystrophin and Dystroglycan become enriched in the ingressing membrane, below the cytokinetic ring, during and after ring constriction. Using multiple alleles, including Dystrophin isoform-specific mutants, we show that Dystrophin/Dystroglycan localization is linked with unanticipated roles in regulating cytokinetic ring contraction and in preventing membrane regression during the abscission period. Altogether, we provide evidence that, rather than opposing cytokinesis completion, the machinery involved in cell-cell and cell-matrix interactions has also evolved functions to ensure cytokinesis efficiency in epithelial tissues.
{"title":"The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia.","authors":"Margarida Gonçalves, Catarina Lopes, Hervé Alégot, Mariana Osswald, Floris Bosveld, Carolina Ramos, Graziella Richard, Yohanns Bellaiche, Vincent Mirouse, Eurico Morais-de-Sá","doi":"10.1038/s44319-024-00319-y","DOIUrl":"https://doi.org/10.1038/s44319-024-00319-y","url":null,"abstract":"<p><p>Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium. Strikingly, this unveiled adhesion molecules and transmembrane receptors that facilitate cytokinesis completion. Among these is Dystroglycan, which connects the extracellular matrix to the cytoskeleton via Dystrophin. Live imaging revealed that Dystrophin and Dystroglycan become enriched in the ingressing membrane, below the cytokinetic ring, during and after ring constriction. Using multiple alleles, including Dystrophin isoform-specific mutants, we show that Dystrophin/Dystroglycan localization is linked with unanticipated roles in regulating cytokinetic ring contraction and in preventing membrane regression during the abscission period. Altogether, we provide evidence that, rather than opposing cytokinesis completion, the machinery involved in cell-cell and cell-matrix interactions has also evolved functions to ensure cytokinesis efficiency in epithelial tissues.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1038/s44319-024-00308-1
James W Bryson, Ülkü Uzun, Victor O Oria, Jamie Y Auxillos, Iman Safari, Alexia M Lopresti, Agnieszka Krzyzanowska, Katrine Sonne-Hansen
{"title":"Cultivating the next generation of leaders : How postdocs, principal investigators and institutes can nurture and select for leadership competencies.","authors":"James W Bryson, Ülkü Uzun, Victor O Oria, Jamie Y Auxillos, Iman Safari, Alexia M Lopresti, Agnieszka Krzyzanowska, Katrine Sonne-Hansen","doi":"10.1038/s44319-024-00308-1","DOIUrl":"https://doi.org/10.1038/s44319-024-00308-1","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}