Chlamydia trachomatis serovars are obligate intracellular bacterial pathogens mainly causing ocular and urogenital infections that affect millions of people worldwide and which can lead to blindness or sterility. They reside and multiply intracellularly within a membrane-bound vacuolar compartment, known as inclusion, and are characterized by a developmental cycle involving two morphologically and physiologically distinct chlamydial forms. Completion of the developmental cycle involves the secretion of > 70 C. trachomatis proteins that function in the host cell cytoplasm and nucleus, in the inclusion membrane and lumen, and in the extracellular milieu. These proteins can, for example, interfere with the host cell cytoskeleton, vesicular and non-vesicular transport, metabolism, and immune signalling. Generally, this promotes C. trachomatis invasion into, and escape from, host cells, the acquisition of nutrients by the chlamydiae, and evasion of cell-autonomous, humoral and cellular innate immunity. Here, we present an in-depth review on the current knowledge and outstanding questions about these C. trachomatis secreted proteins.
{"title":"The multiple functions of the numerous Chlamydia trachomatis secreted proteins: the tip of the iceberg","authors":"Joana N. Bugalhão, L. J. Mota","doi":"10.15698/mic2019.09.691","DOIUrl":"https://doi.org/10.15698/mic2019.09.691","url":null,"abstract":"Chlamydia trachomatis serovars are obligate intracellular bacterial pathogens mainly causing ocular and urogenital infections that affect millions of people worldwide and which can lead to blindness or sterility. They reside and multiply intracellularly within a membrane-bound vacuolar compartment, known as inclusion, and are characterized by a developmental cycle involving two morphologically and physiologically distinct chlamydial forms. Completion of the developmental cycle involves the secretion of > 70 C. trachomatis proteins that function in the host cell cytoplasm and nucleus, in the inclusion membrane and lumen, and in the extracellular milieu. These proteins can, for example, interfere with the host cell cytoskeleton, vesicular and non-vesicular transport, metabolism, and immune signalling. Generally, this promotes C. trachomatis invasion into, and escape from, host cells, the acquisition of nutrients by the chlamydiae, and evasion of cell-autonomous, humoral and cellular innate immunity. Here, we present an in-depth review on the current knowledge and outstanding questions about these C. trachomatis secreted proteins.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"414 - 449"},"PeriodicalIF":4.6,"publicationDate":"2019-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49309772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jordan Gulli, E. Cook, Eugene Kroll, Adam P. Rosebrock, A. Caudy, Frank Rosenzweig
Baker's yeast has a finite lifespan and ages in two ways: a mother cell can only divide so many times (its replicative lifespan), and a non-dividing cell can only live so long (its chronological lifespan). Wild and laboratory yeast strains exhibit natural variation for each type of lifespan, and the genetic basis for this variation has been generalized to other eukaryotes, including metazoans. To date, yeast chronological lifespan has chiefly been studied in relation to the rate and mode of functional decline among non-dividing cells in nutrient-depleted batch culture. However, this culture method does not accurately capture two major classes of long-lived metazoan cells: cells that are terminally differentiated and metabolically active for periods that approximate animal lifespan (e.g. cardiac myocytes), and cells that are pluripotent and metabolically quiescent (e.g. stem cells). Here, we consider alternative ways of cultivating Saccharomyces cerevisiae so that these different metabolic states can be explored in non-dividing cells: (i) yeast cultured as giant colonies on semi-solid agar, (ii) yeast cultured in retentostats and provided sufficient nutrients to meet minimal energy requirements, and (iii) yeast encapsulated in a semisolid matrix and fed ad libitum in bioreactors. We review the physiology of yeast cultured under each of these conditions, and explore their potential to provide unique insights into determinants of chronological lifespan in the cells of higher eukaryotes.
{"title":"Diverse conditions support near-zero growth in yeast: Implications for the study of cell lifespan","authors":"Jordan Gulli, E. Cook, Eugene Kroll, Adam P. Rosebrock, A. Caudy, Frank Rosenzweig","doi":"10.15698/mic2019.09.690","DOIUrl":"https://doi.org/10.15698/mic2019.09.690","url":null,"abstract":"Baker's yeast has a finite lifespan and ages in two ways: a mother cell can only divide so many times (its replicative lifespan), and a non-dividing cell can only live so long (its chronological lifespan). Wild and laboratory yeast strains exhibit natural variation for each type of lifespan, and the genetic basis for this variation has been generalized to other eukaryotes, including metazoans. To date, yeast chronological lifespan has chiefly been studied in relation to the rate and mode of functional decline among non-dividing cells in nutrient-depleted batch culture. However, this culture method does not accurately capture two major classes of long-lived metazoan cells: cells that are terminally differentiated and metabolically active for periods that approximate animal lifespan (e.g. cardiac myocytes), and cells that are pluripotent and metabolically quiescent (e.g. stem cells). Here, we consider alternative ways of cultivating Saccharomyces cerevisiae so that these different metabolic states can be explored in non-dividing cells: (i) yeast cultured as giant colonies on semi-solid agar, (ii) yeast cultured in retentostats and provided sufficient nutrients to meet minimal energy requirements, and (iii) yeast encapsulated in a semisolid matrix and fed ad libitum in bioreactors. We review the physiology of yeast cultured under each of these conditions, and explore their potential to provide unique insights into determinants of chronological lifespan in the cells of higher eukaryotes.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"397 - 413"},"PeriodicalIF":4.6,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43562953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The formation of new ribosomes is a fundamental cellular process for each living cell and is tightly interwoven with cell cycle control and proliferation. Minimal disturbances of this pathway can result in ribosomopathies including an increased risk for certain cancer types. Thus, targeting ribosome biogenesis is an emerging strategy in cancer therapy. However, due to its complex nature, we are only at the beginning to understand the dynamics of the ribosome biogenesis pathway. One arising approach that will help us to embrace the tight timely cascade of events that is needed to form a new ribosome is the use of targeted chemical inhibition. However, only very few specific chemical inhibitors of the ribosome biogenesis pathway have been identified so far. Here we review our recently published screen to identify novel inhibitors of the ribosome biogenesis pathway in yeast (Awad et al., 2019, BMC Biology). These inhibitors can provide novel tools for basic research and can serve as starting-points to develop new chemotherapeutics.
新核糖体的形成是每个活细胞的基本细胞过程，与细胞周期控制和增殖紧密交织在一起。该途径的最小干扰可导致核糖体疾病，包括增加某些癌症类型的风险。因此，靶向核糖体生物发生是癌症治疗中的一种新兴策略。然而，由于其复杂性，我们才刚刚开始了解核糖体生物发生途径的动力学。一种新兴的方法是使用靶向化学抑制，它将帮助我们接受形成新核糖体所需的紧密及时的级联事件。然而，到目前为止，只有极少数核糖体生物发生途径的特异性化学抑制剂被鉴定出来。在这里，我们回顾了我们最近发表的筛选，以确定酵母中核糖体生物发生途径的新抑制剂（Awad et al.，2019，BMC Biology）。这些抑制剂可以为基础研究提供新的工具，并可以作为开发新的化疗药物的起点。
{"title":"Inhibiting eukaryotic ribosome biogenesis: Mining new tools for basic research and medical applications.","authors":"Lisa Kofler, Michael Prattes, Helmut Bergler","doi":"10.15698/mic2019.10.695","DOIUrl":"10.15698/mic2019.10.695","url":null,"abstract":"<p><p>The formation of new ribosomes is a fundamental cellular process for each living cell and is tightly interwoven with cell cycle control and proliferation. Minimal disturbances of this pathway can result in ribosomopathies including an increased risk for certain cancer types. Thus, targeting ribosome biogenesis is an emerging strategy in cancer therapy. However, due to its complex nature, we are only at the beginning to understand the dynamics of the ribosome biogenesis pathway. One arising approach that will help us to embrace the tight timely cascade of events that is needed to form a new ribosome is the use of targeted chemical inhibition. However, only very few specific chemical inhibitors of the ribosome biogenesis pathway have been identified so far. Here we review our recently published screen to identify novel inhibitors of the ribosome biogenesis pathway in yeast (Awad <i>et al.</i>, 2019, BMC Biology). These inhibitors can provide novel tools for basic research and can serve as starting-points to develop new chemotherapeutics.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"491-493"},"PeriodicalIF":4.1,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46011273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. R. Georgescu, Matías Capella, Sabine Fischer-Burkart, Sigurd Braun
Maintaining the identity of chromatin states requires mechanisms that ensure their structural integrity through the concerted actions of histone modifiers, readers, and erasers. Histone H3K9me and H3K27me are hallmarks of repressed heterochromatin, whereas H3K4me and H3K36me are associated with actively transcribed euchromatin. Paradoxically, several studies have reported that loss of Set2, the methyltransferase responsible for H3K36me, causes de-repression of heterochromatin. Here we show that unconstrained activity of the acetyltransferase complex Mst2C, which antagonizes heterochromatin, is the main cause of the silencing defects observed in Set2-deficient cells. As previously shown, Mst2C is sequestered to actively transcribed chromatin via binding to H3K36me3 that is recognized by the PWWP domain protein Pdp3. We demonstrate that combining deletions of set2+ and pdp3+ results in an epistatic silencing phenotype. In contrast, deleting mst2+, or other members of Mst2C, fully restores silencing in Set2-deficient cells. Suppression of the silencing defect in set2Δ cells is specific for pericentromeres and subtelomeres, which are marked by H3K9me, but not seen for loci that lack genuine heterochromatin. Although Mst2 catalyzes acetylation of H3K14, this modification is likely not involved in the Set2-dependent pathway due to redundancy with the HAT Gcn5. Moreover, while Mst2 is required for acetylation of the H2B ubiquitin ligase Brl1 in euchromatin, we find that its role in heterochromatin silencing is not affected by Brl1 acetylation. We propose that it targets another, unknown substrate critical for heterochromatin silencing. Our findings demonstrate that maintenance of chromatin states requires spatial constraint of opposing chromatin activities.
{"title":"The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast","authors":"P. R. Georgescu, Matías Capella, Sabine Fischer-Burkart, Sigurd Braun","doi":"10.1101/738096","DOIUrl":"https://doi.org/10.1101/738096","url":null,"abstract":"Maintaining the identity of chromatin states requires mechanisms that ensure their structural integrity through the concerted actions of histone modifiers, readers, and erasers. Histone H3K9me and H3K27me are hallmarks of repressed heterochromatin, whereas H3K4me and H3K36me are associated with actively transcribed euchromatin. Paradoxically, several studies have reported that loss of Set2, the methyltransferase responsible for H3K36me, causes de-repression of heterochromatin. Here we show that unconstrained activity of the acetyltransferase complex Mst2C, which antagonizes heterochromatin, is the main cause of the silencing defects observed in Set2-deficient cells. As previously shown, Mst2C is sequestered to actively transcribed chromatin via binding to H3K36me3 that is recognized by the PWWP domain protein Pdp3. We demonstrate that combining deletions of set2+ and pdp3+ results in an epistatic silencing phenotype. In contrast, deleting mst2+, or other members of Mst2C, fully restores silencing in Set2-deficient cells. Suppression of the silencing defect in set2Δ cells is specific for pericentromeres and subtelomeres, which are marked by H3K9me, but not seen for loci that lack genuine heterochromatin. Although Mst2 catalyzes acetylation of H3K14, this modification is likely not involved in the Set2-dependent pathway due to redundancy with the HAT Gcn5. Moreover, while Mst2 is required for acetylation of the H2B ubiquitin ligase Brl1 in euchromatin, we find that its role in heterochromatin silencing is not affected by Brl1 acetylation. We propose that it targets another, unknown substrate critical for heterochromatin silencing. Our findings demonstrate that maintenance of chromatin states requires spatial constraint of opposing chromatin activities.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 1","pages":"80 - 92"},"PeriodicalIF":4.6,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47254645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In our recent publication (Zhang et al., 2019), we demonstrate an interesting mode of regulation of purine metabolism unique to Proteobacteria. In this microreview, we would like to reflect on the ideas put forward, with special focus on protein domain architecture of the enzyme involved, its orthologues in plants, and the implications of the differential effects observed between binding of the two alarmone molecules, ppGpp (guanosine 3′,5′-bisdiphosphate) and pppGpp (guanosine-5′-triphosphate-3′-diphosphate). In our previous work, we showed that the Escherichia coli nucleotide 5'-monophosphate nucleosidase, PpnN, which is conserved in Proteobacteria, cleaves its preferred substrate, guanosine monophosphate (GMP), at a much higher rate in the presence of both pppGpp and ppGpp (Figure 1A). Structural analysis reveals that binding of pppGpp leads to a conformational change in the protein that exposes its active site, suggesting this is the reason for the observed increase in activity. Finally, point mutation of the alarmone-interacting residues show a defect in binding, resulting in (i) increased basal catalytic activity of PpnN and higher competitive fitness of E. coli in an environment with fluctuating nutrient levels, and (ii) increased bacterial sensitivity towards antibiotics. In contrast, complete loss of the ppnN gene has the inverse effect, i.e. reduced competitive growth and improved antibiotic tolerance. We used these observations to propose a model in which E. coli uses PpnN to balance the need of fitness (fast growth) against tolerance towards antibiotics to improve survival.
在我们最近的出版物（Zhang et al.，2019）中，我们展示了变形杆菌特有的嘌呤代谢调控模式。在这篇微综述中，我们想反思所提出的观点，特别关注所涉及的酶的蛋白质结构域结构、其在植物中的同源物，以及观察到的两种鸟嘌呤分子ppGpp（鸟苷3′，5′-二磷酸）和pppGpp（鸟苷5′-三磷酸-3′-二磷酸盐）结合之间的差异效应的含义。在我们之前的工作中，我们发现在变形杆菌中保守的大肠杆菌核苷酸5'-单磷酸核苷酶PpnN在pppGpp和ppGpp存在的情况下，以更高的速率切割其首选底物鸟苷（GMP）（图1A）。结构分析表明，pppGpp的结合导致暴露其活性位点的蛋白质的构象变化，这表明这是观察到的活性增加的原因。最后，alarmone相互作用残基的点突变显示出结合缺陷，导致（i）PpnN的基础催化活性增加，大肠杆菌在营养水平波动的环境中具有更高的竞争适应性，以及（ii）细菌对抗生素的敏感性增加。相反，ppnN基因的完全缺失具有相反的效果，即减少竞争性生长和提高抗生素耐受性。我们利用这些观察结果提出了一个模型，在该模型中，大肠杆菌使用PpnN来平衡适应度（快速生长）的需求和对抗生素的耐受性，以提高生存率。
{"title":"Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response","authors":"René L. Bærentsen, D. Brodersen, Y. Zhang","doi":"10.15698/mic2019.09.692","DOIUrl":"https://doi.org/10.15698/mic2019.09.692","url":null,"abstract":"In our recent publication (Zhang et al., 2019), we demonstrate an interesting mode of regulation of purine metabolism unique to Proteobacteria. In this microreview, we would like to reflect on the ideas put forward, with special focus on protein domain architecture of the enzyme involved, its orthologues in plants, and the implications of the differential effects observed between binding of the two alarmone molecules, ppGpp (guanosine 3′,5′-bisdiphosphate) and pppGpp (guanosine-5′-triphosphate-3′-diphosphate). In our previous work, we showed that the Escherichia coli nucleotide 5'-monophosphate nucleosidase, PpnN, which is conserved in Proteobacteria, cleaves its preferred substrate, guanosine monophosphate (GMP), at a much higher rate in the presence of both pppGpp and ppGpp (Figure 1A). Structural analysis reveals that binding of pppGpp leads to a conformational change in the protein that exposes its active site, suggesting this is the reason for the observed increase in activity. Finally, point mutation of the alarmone-interacting residues show a defect in binding, resulting in (i) increased basal catalytic activity of PpnN and higher competitive fitness of E. coli in an environment with fluctuating nutrient levels, and (ii) increased bacterial sensitivity towards antibiotics. In contrast, complete loss of the ppnN gene has the inverse effect, i.e. reduced competitive growth and improved antibiotic tolerance. We used these observations to propose a model in which E. coli uses PpnN to balance the need of fitness (fast growth) against tolerance towards antibiotics to improve survival.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"450 - 453"},"PeriodicalIF":4.6,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45253467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ability to sense external mechanical stimuli is vital for all organisms. Integrins are transmembrane receptors that mediate bidirectional signalling between the extracellular matrix (ECM) and the cytoskeleton in animals. Thus, integrins can sense changes in ECM mechanics and can translate these into internal biochemical responses through different signalling pathways. In the model yeast species Saccharomyces cerevisiae there are no proteins with sequence similarity to mammalian integrins. However, we here emphasise that the WSC-type (Wsc1, Wsc2, and Wsc3) and the MID-type (Mid2 and Mtl1) mechanosensors in yeast act as partial functional integrin analogues. Various environmental cues recognised by these mechanosensors are transmitted by a conserved signal transduction cascade commonly referred to as the PKC1-SLT1 cell wall integrity (CWI) pathway. We exemplify the WSC- and MID-type mechanosensors functional analogy to integrins with a number of studies where they resemble the integrins in terms of both mechanistic and molecular features as well as in the overall phenotypic consequences of their activity. In addition, many important components in integrin-dependent signalling in humans are conserved in yeast; for example, Sla1 and Sla2 are homologous to different parts of human talin, and we propose that they together might be functionally similar to talin. We also propose that the yeast cell wall is a prominent cellular feature involved in sensing a number of external factors and subsequently activating different signalling pathways. In a hypothetical model, we propose that nutrient limitations modulate cell wall elasticity, which is sensed by the mechanosensors and results in filamentous growth. We believe that mechanosensing is a somewhat neglected aspect of yeast biology, and we argue that the physiological and molecular consequences of signal transduction initiated at the cell wall deserve more attention.
{"title":"Integrins in disguise - mechanosensors in Saccharomyces cerevisiae as functional integrin analogues","authors":"Tarek Elhasi, A. Blomberg","doi":"10.15698/mic2019.08.686","DOIUrl":"https://doi.org/10.15698/mic2019.08.686","url":null,"abstract":"The ability to sense external mechanical stimuli is vital for all organisms. Integrins are transmembrane receptors that mediate bidirectional signalling between the extracellular matrix (ECM) and the cytoskeleton in animals. Thus, integrins can sense changes in ECM mechanics and can translate these into internal biochemical responses through different signalling pathways. In the model yeast species Saccharomyces cerevisiae there are no proteins with sequence similarity to mammalian integrins. However, we here emphasise that the WSC-type (Wsc1, Wsc2, and Wsc3) and the MID-type (Mid2 and Mtl1) mechanosensors in yeast act as partial functional integrin analogues. Various environmental cues recognised by these mechanosensors are transmitted by a conserved signal transduction cascade commonly referred to as the PKC1-SLT1 cell wall integrity (CWI) pathway. We exemplify the WSC- and MID-type mechanosensors functional analogy to integrins with a number of studies where they resemble the integrins in terms of both mechanistic and molecular features as well as in the overall phenotypic consequences of their activity. In addition, many important components in integrin-dependent signalling in humans are conserved in yeast; for example, Sla1 and Sla2 are homologous to different parts of human talin, and we propose that they together might be functionally similar to talin. We also propose that the yeast cell wall is a prominent cellular feature involved in sensing a number of external factors and subsequently activating different signalling pathways. In a hypothetical model, we propose that nutrient limitations modulate cell wall elasticity, which is sensed by the mechanosensors and results in filamentous growth. We believe that mechanosensing is a somewhat neglected aspect of yeast biology, and we argue that the physiological and molecular consequences of signal transduction initiated at the cell wall deserve more attention.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"335 - 355"},"PeriodicalIF":4.6,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42503262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sulfur assimilation and the biosynthesis of methionine, cysteine and S-adenosylmethionine (SAM) are critical to life. As a cofactor, SAM is required for the activity of most methyltransferases (MTases) and as such has broad impact on diverse cellular processes. Assigning function to MTases remains a challenge however, as many MTases are partially redundant, they often have multiple cellular roles and these activities can be condition-dependent. To address these challenges, we performed a systematic synthetic genetic analysis of all pairwise MTase double mutations in normal and stress conditions (16°C, 37°C, and LiCl) resulting in an unbiased comprehensive overview of the complexity and plasticity of the methyltransferome. Based on this network, we performed biochemical analysis of members of the histone H3K4 COMPASS complex and the phospholipid methyltransferase OPI3 to reveal a new role for a phospholipid methyltransferase in mediating histone methylation (H3K4) which underscores a potential link between lipid homeostasis and histone methylation. Our findings provide a valuable resource to study methyltransferase function, the dynamics of the methyltransferome, genetic crosstalk between biological processes and the dynamics of the methyltransferome in response to cellular stress.
{"title":"Network dynamics of the yeast methyltransferome","authors":"G. Giaever, Elena Lissina, C. Nislow","doi":"10.15698/mic2019.08.687","DOIUrl":"https://doi.org/10.15698/mic2019.08.687","url":null,"abstract":"Sulfur assimilation and the biosynthesis of methionine, cysteine and S-adenosylmethionine (SAM) are critical to life. As a cofactor, SAM is required for the activity of most methyltransferases (MTases) and as such has broad impact on diverse cellular processes. Assigning function to MTases remains a challenge however, as many MTases are partially redundant, they often have multiple cellular roles and these activities can be condition-dependent. To address these challenges, we performed a systematic synthetic genetic analysis of all pairwise MTase double mutations in normal and stress conditions (16°C, 37°C, and LiCl) resulting in an unbiased comprehensive overview of the complexity and plasticity of the methyltransferome. Based on this network, we performed biochemical analysis of members of the histone H3K4 COMPASS complex and the phospholipid methyltransferase OPI3 to reveal a new role for a phospholipid methyltransferase in mediating histone methylation (H3K4) which underscores a potential link between lipid homeostasis and histone methylation. Our findings provide a valuable resource to study methyltransferase function, the dynamics of the methyltransferome, genetic crosstalk between biological processes and the dynamics of the methyltransferome in response to cellular stress.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"356 - 369"},"PeriodicalIF":4.6,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48252012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. M. Salek, F. Carrara, Vicente I. Fernandez, R. Stocker
Chemotaxis allows microorganisms to exploit gradients in chemical stimuli to find nutrient resources and hosts or escape noxious substances. Thus, the life of individual microbes in their natural environments is a continual sequence of decisions based on the perceived chemical gradients. However, it has remained unclear to what extent the chemotaxis properties vary among cells of one species, and whether there is a spectrum of different ‘decision makers' within populations of bacteria. In our recent study (Salek, Carrara et al., Nature Communications 10 (1), 1877), we combine microfluidic experiments with mathematical modeling to demonstrate that even in clonal populations, bacteria are individuals with different abilities to climb chemical gradients.
{"title":"Bacterial maze runners reveal hidden diversity in chemotactic performance","authors":"M. M. Salek, F. Carrara, Vicente I. Fernandez, R. Stocker","doi":"10.15698/mic2019.08.688","DOIUrl":"https://doi.org/10.15698/mic2019.08.688","url":null,"abstract":"Chemotaxis allows microorganisms to exploit gradients in chemical stimuli to find nutrient resources and hosts or escape noxious substances. Thus, the life of individual microbes in their natural environments is a continual sequence of decisions based on the perceived chemical gradients. However, it has remained unclear to what extent the chemotaxis properties vary among cells of one species, and whether there is a spectrum of different ‘decision makers' within populations of bacteria. In our recent study (Salek, Carrara et al., Nature Communications 10 (1), 1877), we combine microfluidic experiments with mathematical modeling to demonstrate that even in clonal populations, bacteria are individuals with different abilities to climb chemical gradients.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"370 - 372"},"PeriodicalIF":4.6,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45898450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandre Légiot, C. Céré, Thibaud Dupoiron, Mohamed Kaabouni, N. Camougrand, S. Manon
The distribution of the pro-apoptotic protein Bax in the outer mitochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.
{"title":"Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release","authors":"Alexandre Légiot, C. Céré, Thibaud Dupoiron, Mohamed Kaabouni, N. Camougrand, S. Manon","doi":"10.1101/443606","DOIUrl":"https://doi.org/10.1101/443606","url":null,"abstract":"The distribution of the pro-apoptotic protein Bax in the outer mitochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"6 1","pages":"257 - 266"},"PeriodicalIF":4.6,"publicationDate":"2018-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43411868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theodora Sideri, Yoko Yashiroda, David A Ellis, María Rodríguez-López, Minoru Yoshida, M. Tuite, J. Bähler
Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-forming proteins exist in S. cerevisiae, [HET-s] of Podospora anserina is the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeast Schizosaccharomyces pombe. We show that S. pombe cells can support the formation and maintenance of the prion form of the S. cerevisiae Sup35 translation factor [PSI+], and that the formation and propagation of these Sup35 aggregates is inhibited by guanidine hydrochloride, indicating commonalities in prion propagation machineries in these evolutionary diverged yeasts. A proteome-wide screen identified the Ctr4 copper transporter subunit as a putative prion with a predicted prion-like domain. Overexpression of the ctr4 gene resulted in large Ctr4 protein aggregates that were both detergent and proteinase-K resistant. Cells carrying such [CTR+] aggregates showed increased sensitivity to oxidative stress, and this phenotype could be transmitted to aggregate-free [ctr-] cells by transformation with [CTR+] cell extracts. Moreover, this [CTR+] phenotype was inherited in a non-Mendelian manner following mating with naïve [ctr-] cells, but intriguingly the [CTR+] phenotype was not eliminated by guanidine-hydrochloride treatment. Thus, Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi.
{"title":"The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe","authors":"Theodora Sideri, Yoko Yashiroda, David A Ellis, María Rodríguez-López, Minoru Yoshida, M. Tuite, J. Bähler","doi":"10.15698/mic2017.01.552","DOIUrl":"https://doi.org/10.15698/mic2017.01.552","url":null,"abstract":"Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-forming proteins exist in S. cerevisiae, [HET-s] of Podospora anserina is the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeast Schizosaccharomyces pombe. We show that S. pombe cells can support the formation and maintenance of the prion form of the S. cerevisiae Sup35 translation factor [PSI+], and that the formation and propagation of these Sup35 aggregates is inhibited by guanidine hydrochloride, indicating commonalities in prion propagation machineries in these evolutionary diverged yeasts. A proteome-wide screen identified the Ctr4 copper transporter subunit as a putative prion with a predicted prion-like domain. Overexpression of the ctr4 gene resulted in large Ctr4 protein aggregates that were both detergent and proteinase-K resistant. Cells carrying such [CTR+] aggregates showed increased sensitivity to oxidative stress, and this phenotype could be transmitted to aggregate-free [ctr-] cells by transformation with [CTR+] cell extracts. Moreover, this [CTR+] phenotype was inherited in a non-Mendelian manner following mating with naïve [ctr-] cells, but intriguingly the [CTR+] phenotype was not eliminated by guanidine-hydrochloride treatment. Thus, Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"4 1","pages":"16 - 28"},"PeriodicalIF":4.6,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47138494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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