RESUMEN
Compartmentation is essential for the localization of biological processes within a cell. In 2010, three groups independently reported that cytidine triphosphate synthase (CTPS), a metabolic enzyme for de novo synthesis of the nucleotide CTP, is compartmentalized in cytoophidia (Greek for "cellular snakes") in bacteria, yeast, and fruit flies. Subsequent studies demonstrate that CTPS can also form filaments in human cells. Thus, the cytoophidium represents a new type of intracellular compartment that is strikingly conserved across prokaryotes and eukaryotes. Multiple lines of evidence have recently suggested that polymerization of metabolic enzymes such as CTPS and inosine monophosphate dehydrogenase into filamentous cytoophidia modulates enzymatic activity. With many more metabolic enzymes found to form the cytoophidium and its kind, compartmentation via filamentation may serve as a general mechanism for the regulation of metabolism.
Asunto(s)
Compartimento Celular , Enzimas/metabolismo , Animales , Humanos , Modelos BiológicosRESUMEN
Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.
Asunto(s)
Progesterona , Receptores de Progesterona , Femenino , Ratones , Humanos , Animales , Progesterona/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Implantación del Embrión/genética , Útero/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones Noqueados , ARN Mensajero/metabolismoRESUMEN
As an information bridge between DNA and protein, RNA regulates cellular processes and gene expression in various ways. From its synthesis to degradation, RNA is associated with a range of RNA-binding proteins. Therefore, it is necessary to develop innovative methods to study the interaction between RNA and proteins. Previously, we developed an RNA-centric method, called CRISPR-based RNA-United Interacting System (CRUIS), to capture RNA-protein interaction in cells. On this basis, here we develop an enhanced CRUIS (eCRUIS) by combining the power of dCas13d and the engineered promiscuous ligase TurboID. The current version allows us to rapidly label RNA-binding proteins on the target RNA within 30 minutes, potentially for in vivo use. By introducing bait-assay with exogenous RNA, we confirm that eCRUIS can effectively label RNA-binding proteins on bait RNA in a short time. eCRUIS provides a broader range of in vitro and in vivo applications for studying RNA-protein interactions.
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Sistemas CRISPR-Cas , Proteínas de Unión al ARN , Humanos , Sistemas CRISPR-Cas/genética , Células HEK293 , Unión Proteica , ARN/metabolismo , ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
The cytoophidium is an evolutionarily conserved subcellular structure formed by filamentous polymers of metabolic enzymes. In vertebrates, inosine monophosphate dehydrogenase (IMPDH), which catalyses the rate-limiting step in guanosine triphosphate (GTP) biosynthesis, is one of the best-known cytoophidium-forming enzymes. Formation of the cytoophidium has been proposed to alleviate the inhibition of IMPDH, thereby facilitating GTP production to support the rapid proliferation of certain cell types such as lymphocytes, cancer cells and pluripotent stem cells (PSCs). However, past studies lacked appropriate models to elucidate the significance of IMPDH cytoophidium under normal physiological conditions. In this study, we demonstrate that the presence of IMPDH cytoophidium in mouse PSCs correlates with their metabolic status rather than pluripotency. By introducing IMPDH2 Y12C point mutation through genome editing, we established mouse embryonic stem cell (ESC) lines incapable of forming IMPDH polymers and the cytoophidium. Our data indicate an important role of IMPDH cytoophidium in sustaining a positive feedback loop that couples nucleotide biosynthesis with upstream metabolic pathways. Additionally, we find that IMPDH2 Y12C mutation leads to decreased cell proliferation and increased DNA damage in teratomas, as well as impaired embryo development following blastocoel injection. Further analysis shows that IMPDH cytoophidium assembly in mouse embryonic development begins after implantation and gradually increases throughout fetal development. These findings provide insights into the regulation of IMPDH polymerisation in embryogenesis and its significance in coordinating cell metabolism and development.
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Proliferación Celular , IMP Deshidrogenasa , Animales , Femenino , Ratones , Daño del ADN , Desarrollo Fetal/genética , Guanosina Trifosfato/metabolismo , IMP Deshidrogenasa/metabolismo , IMP Deshidrogenasa/genética , Ratones Endogámicos C57BL , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Estructuras Celulares/metabolismoRESUMEN
Spinal muscular atrophy (SMA) is the most common autosomal recessive neurodegenerative disease, and is characterised by spinal motor neuron loss, impaired motor function and, often, premature death. Mutations and deletions in the widely expressed survival motor neuron 1 (SMN1) gene cause SMA; however, the mechanisms underlying the selectivity of motor neuron degeneration are not well understood. Although SMA is degenerative in nature, SMN function during embryonic and early postnatal development appears to be essential for motor neuron survival in animal models and humans. Notwithstanding, how developmental defects contribute to the subversion of postnatal and adult motor function remains elusive. Here, in a Drosophila SMA model, we show that neurodevelopmental defects precede gross locomotor dysfunction in larvae. Furthermore, to specifically address the relevance of SMN during neurogenesis and in neurogenic cell types, we show that SMN knockdown using neuroblast-specific and pan-neuronal drivers, but not differentiated neuron or glial cell drivers, impairs adult motor function. Using targeted knockdown, we further restricted SMN manipulation in neuroblasts to a defined time window. Our aim was to express specifically in the neuronal progenitor cell types that have not formed synapses, and thus a time that precedes neuromuscular junction formation and maturation. By restoring SMN levels in these distinct neuronal population, we partially rescue the larval locomotor defects of Smn mutants. Finally, combinatorial SMN knockdown in immature and mature neurons synergistically enhances the locomotor and survival phenotypes. Our in-vivo study is the first to directly rescue the motor defects of an SMA model by expressing Smn in an identifiable population of Drosophila neuroblasts and developing neurons, highlighting that neuronal sensitivity to SMN loss may arise before synapse establishment and nerve cell maturation.
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Atrofia Muscular Espinal , Enfermedades Neurodegenerativas , Animales , Modelos Animales de Enfermedad , Drosophila/genética , Humanos , Neuronas Motoras/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Neurogénesis/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismoRESUMEN
Although most cells are mononuclear, the nucleus can exist in the form of binucleate or even multinucleate to respond to different physiological processes. The male accessory gland of Drosophila is the organ that produces semen, and its main cells are binucleate. Here we observe that CTP synthase (CTPS) forms filamentous cytoophidia in binuclear main cells, primarily located at the cell boundary. In CTPSH355A, a point mutation that destroys the formation of cytoophidia, we find that the nucleation mode of the main cells changes, including mononucleates and vertical distribution of binucleates. Although the overexpression of CTPSH355A can restore the level of CTPS protein, it will neither form cytoophidia nor eliminate the abnormal nucleation pattern. Therefore, our data indicate that there is an unexpected functional link between the formation of cytoophidia and the maintenance of binucleation in Drosophila main cells.
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Ligasas de Carbono-Nitrógeno , Drosophila , Animales , Masculino , Ligasas de Carbono-Nitrógeno/genética , Ligasas de Carbono-Nitrógeno/metabolismo , Núcleo Celular/metabolismo , Citoesqueleto/metabolismo , Drosophila/metabolismoRESUMEN
Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is regulated by the binding of four nucleotides and glutamine. While glutamine serves as an ammonia donor for the ATP-dependent conversion of UTP to CTP, the fourth nucleotide GTP acts as an allosteric activator. Models have been proposed to explain the mechanisms of action at the active site of the ammonia ligase domain and the conformational changes derived by GTP binding. However, actual GTP/ATP/UTP binding modes and relevant conformational changes have not been revealed fully. Here, we report the discovery of binding modes of four nucleotides and a glutamine analog 6-diazo-5-oxo-L-norleucine in Drosophila CTPS by cryo-electron microscopy with near-atomic resolution. Interactions between GTP and surrounding residues indicate that GTP acts to coordinate reactions at both domains by directly blocking ammonia leakage and stabilizing the ammonia tunnel. Additionally, we observe the ATP-dependent UTP phosphorylation intermediate and determine interacting residues at the ammonia ligase. A noncanonical CTP binding at the ATP binding site suggests another layer of feedback inhibition. Our findings not only delineate the structure of CTPS in the presence of all substrates but also complete our understanding of the underlying mechanisms of the allosteric regulation and CTP synthesis.
Asunto(s)
Adenosina Trifosfato/metabolismo , Amoníaco/metabolismo , Ligasas de Carbono-Nitrógeno/química , Ligasas de Carbono-Nitrógeno/metabolismo , Drosophila melanogaster/enzimología , Glutamina/metabolismo , Uridina Trifosfato/metabolismo , Regulación Alostérica , Animales , Sitios de Unión , Catálisis , Microscopía por Crioelectrón , Hidrólisis , Cinética , Ligandos , Conformación ProteicaRESUMEN
CTP synthase (CTPS) catalyzes the final step of de novo synthesis of CTP. CTPS was first discovered to form filamentous structures termed cytoophidia in Drosophila ovarian cells. Subsequent studies have shown that cytoophidia are widely present in cells of three life domains. In the Drosophila ovary model, our previous studies mainly focused on the early and middle stages, with less involvement in the later stages. In this work, we focus on the later stages of female germline cells in Drosophila. We use live-cell imaging to capture the continuous dynamics of cytoophidia in Stages 10-12. We notice the heterogeneity of cytoophidia in the two types of germline cells (nurse cells and oocytes), manifested in significant differences in morphology, distribution, and dynamics. Surprisingly, we also find that neighboring nurse cells in the same egg chamber exhibit multiple dynamic patterns of cytoophidia over time. Although the described dynamics may be influenced by the in vitro incubation conditions, our observation provides an initial understanding of the dynamics of cytoophidia during late-stage Drosophila oogenesis.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Drosophila , Animales , Femenino , Oogénesis , Citoesqueleto , OocitosRESUMEN
Cytidine triphosphate synthase (CTPS) forms cytoophidia in all three domains of life. Here we focus on the function of cytoophidia in cell proliferation using Schizosaccharomyces pombe as a model system. We find that converting His359 of CTPS into Ala359 leads to cytoophidium disassembly. By reducing the level of CTPS protein or specific mutation, the loss of cytoophidia prolongs the G2 phase and expands cell size. In addition, the loss-filament mutant of CTPS leads to a decrease in the expression of genes related to G2/M transition and cell growth, including histone chaperone slm9. The overexpression of slm9 alleviates the G2 phase elongation and cell size enlargement induced by CTPS loss-filament mutants. Overall, our results connect cytoophidia with cell cycle and cell size control in Schizosaccharomyces pombe.
Asunto(s)
Schizosaccharomyces , Schizosaccharomyces/genética , Ciclo Celular/genética , División Celular , Proliferación Celular , Fase G2RESUMEN
CTP synthase (CTPS), the rate-limiting enzyme in the de novo synthesis of CTP, assembles into a filamentous structure termed the cytoophidium. The Hippo pathway regulates cell proliferation and apoptosis. The relationship of the nucleotide metabolism with the Hippo pathway is little known. Here, we study the impact of the Hippo pathway on the cytoophidium in Drosophila melanogaster posterior follicle cells (PFCs). We find that the inactivation of the Hippo pathway correlates with reduced cytoophidium length and number within PFCs. During the overexpression of CTPS, the presence of Hippo mutations also reduces the length of cytoophidia in PFCs. In addition, we observe that knocking down CTPS mitigates hpo (Hippo)-associated over-proliferation. In summary, our results suggest that there is a connection between the Hippo pathway and the nucleotide biosynthesis enzyme CTPS in PFCs.
Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Vía de Señalización Hippo , Citoesqueleto/metabolismo , Nucleótidos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
The nucleotide CTP can be synthesized de novo from UTP via the metabolic enzyme CTP synthase (CTPS). As a textbook enzyme, CTPS has been extensively studied for seven decades. However, it came as a surprise when CTPS was found to form snake-shaped mesoscale cytoophidia in fruit fly cells. Since 2010, more and more studies have demonstrated that CTPS can form cytoophidia within the cells across all three domains of life. Oligomers of CTPS form filaments that are undetectable under light microscopy. This review summarizes our current understanding of cytoophidia and filaments, highlighting some basic features such as conservation, morphology and functions of the two levels of CTPS structures.
Asunto(s)
Citoesqueleto , Drosophila , Animales , Citoesqueleto/metabolismo , Nucleótidos/metabolismo , MicroscopíaRESUMEN
CTP synthase (CTPS) catalyzes the final step of de novo synthesis of the nucleotide CTP. In 2010, CTPS has been found to form filamentous structures termed cytoophidia in Drosophila follicle cells and germline cells. Subsequently, cytoophidia have been reported in many species across three domains of life: bacteria, eukaryotes and archaea. Forming cytoophidia appears to be a highly conserved and ancient property of CTPS. To our surprise, here we find that polar cells and stalk cells, two specialized types of cells composing Drosophila interfollicular stalks, do not possess obvious cytoophidia. We show that Myc level is low in these two types of cells. Treatment with a glutamine analog, 6-diazo-5-oxo-l-norleucine (DON), increases cytoophidium assembly in main follicle cells, but not in polar cells or stalk cells. Moreover, overexpressing Myc induces cytoophidium formation in stalk cells. When CTPS is overexpressed, cytoophidia can be observed both in stalk cells and polar cells. Our findings provide an interesting paradigm for the in vivo study of cytoophidium assembly and disassembly among different populations of follicle cells.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Drosophila , Animales , Ligasas de Carbono-Nitrógeno/química , Ligasas de Carbono-Nitrógeno/genética , Células Germinativas , GlutaminaRESUMEN
CTP synthase (CTPS), a metabolic enzyme responsible for the de novo synthesis of CTP, can form filamentous structures termed cytoophidia, which are evolutionarily conserved from bacteria to humans. Here we used Schizosaccharomyces pombe to study the cytoophidium assembly regulation by ubiquitination. We tested the CTP synthase's capacity to be post-translationally modified by ubiquitin or be affected by the ubiquitination state of the cell and showed that ubiquitination is important for the maintenance of the CTPS filamentous structure in fission yeast. We have identified proteins which are in complex with CTPS, including specific ubiquitination regulators which significantly affect CTPS filamentation, and mapped probable ubiquitination targets on CTPS. Furthermore, we discovered that a cohort of deubiquitinating enzymes is important for the regulation of cytoophidium's filamentous morphology. Our study provides a framework for the analysis of the effects that ubiquitination and deubiquitination have on the formation of cytoophidia.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Schizosaccharomyces , Humanos , Ligasas de Carbono-Nitrógeno/metabolismo , Citidina Trifosfato/metabolismo , Enzimas Desubicuitinizantes/metabolismo , Schizosaccharomyces/metabolismo , Ubiquitinación , Ubiquitinas/metabolismoRESUMEN
CTP synthase (CTPS), the enzyme responsible for the last step of de novo synthesis of CTP, forms filamentous structures termed cytoophidia in all three domains of life. Here we report that oncogenic Ras regulates cytoophidium formation in Drosophila intestines. Overexpressing active Ras induces elongate and abundant cytoophidia in intestinal stem cells (ISCs) and enteroblasts (EBs). Knocking-down CTPS in ISCs/EBs suppresses the over- proliferation phenotype induced by ectopic expression of active Ras. Moreover, disrupting cytoophidium formation increases the number of proliferating cells in the background of overexpressing active Ras. Therefore, our results demonstrate a link between Ras and CTPS.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Drosophila , Animales , Ligasas de Carbono-Nitrógeno/genética , Intestinos , Células MadreRESUMEN
The cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.
Asunto(s)
IMP Deshidrogenasa , Espacio Intracelular , Polímeros , Compartimento Celular/fisiología , Humanos , IMP Deshidrogenasa/metabolismo , Espacio Intracelular/metabolismo , Polímeros/metabolismoRESUMEN
Tissue architecture determines its unique physiology and function. How these properties are intertwined has remained unclear. Here we show that the metabolic enzyme CTP synthase (CTPS) form filamentous structures termed cytoophidia along the adipocyte cortex in Drosophila adipose tissue. Loss of cytoophidia, whether due to reduced CTPS expression or a point mutation that specifically abrogates its polymerization ability, causes impaired adipocyte adhesion and defective adipose tissue architecture. Moreover, CTPS influences integrin distribution and dot-like deposition of type IV collagen (Col IV). Col IV-integrin signaling reciprocally regulates the assembly of cytoophidia in adipocytes. Our results demonstrate that a positive feedback signaling loop containing both cytoophidia and integrin adhesion complex couple tissue architecture and metabolism in Drosophila adipose tissue.
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Ligasas de Carbono-Nitrógeno , Colágeno Tipo IV , Animales , Tejido Adiposo/metabolismo , Ligasas de Carbono-Nitrógeno/química , Ligasas de Carbono-Nitrógeno/genética , Ligasas de Carbono-Nitrógeno/metabolismo , Drosophila/metabolismo , IntegrinasRESUMEN
Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in de novo guanine nucleotide biosynthesis. Its activity is negatively regulated by the binding of GTP. IMPDH can form a membraneless subcellular structure termed the cytoophidium in response to certain changes in the metabolic status of the cell. The polymeric form of IMPDH, which is the subunit of the cytoophidium, has been shown to be more resistant to the inhibition by GTP at physiological concentrations, implying a functional correlation between cytoophidium formation and the upregulation of GTP biosynthesis. Herein we demonstrate that zebrafish IMPDH1b and IMPDH2 isoforms can assemble abundant cytoophidium in most of cultured cells under stimuli, while zebrafish IMPDH1a shows distinctive properties of forming the cytoophidium in different cell types. Point mutations that disrupt cytoophidium structure in mammalian models also prevent the aggregation of zebrafish IMPDHs. In addition, we discover the presence of the IMPDH cytoophidium in various tissues of larval and adult fish under normal growth conditions. Our results reveal that polymerization and cytoophidium assembly of IMPDH can be a regulatory machinery conserved among vertebrates, and with specific physiological purposes.
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Estructuras Citoplasmáticas/ultraestructura , IMP Deshidrogenasa/química , Proteínas de Pez Cebra/química , Pez Cebra/metabolismo , Animales , Línea Celular , Estructuras Citoplasmáticas/química , Expresión Génica , Guanosina Trifosfato/biosíntesis , Guanosina Trifosfato/metabolismo , Humanos , IMP Deshidrogenasa/genética , IMP Deshidrogenasa/metabolismo , Isoenzimas/química , Isoenzimas/genética , Mutación Puntual , Regulación hacia Arriba , Pez Cebra/crecimiento & desarrollo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
In most mammalian species, the testis descends from the abdomen into the scrotum during fetal or neonatal life. The failure of testicular descent, a pathological condition known as cryptorchidism, has long been the subject of scientific interest in a wide range of fields, including medicine, developmental biology, and evolutionary biology. In this study, we analyzed global gene expression changes associated with experimental cryptorchidism in mice by using RNA-seq. A total of 453 differentially expressed genes were identified, of which 236 genes were upregulated, and 217 genes were downregulated. Gene ontology, pathway, and gene network analysis highlighted the activation of inflammatory response in experimental cryptorchidism. By examining the promoter regions of differentially expressed genes, we identified 12 causal transcription factors. In addition, we also induced experimental cryptorchidism in two cynomolgus monkeys and performed RNA-seq. A cross-species comparison was performed at the gene expression level. Our study provides a valuable resource for further understanding the molecular mechanisms of cryptorchidism in mammals.
Asunto(s)
Criptorquidismo , Animales , Criptorquidismo/genética , Criptorquidismo/metabolismo , Criptorquidismo/patología , Perfilación de la Expresión Génica , Humanos , Macaca fascicularis/genética , Masculino , Mamíferos/genética , Testículo/metabolismo , Transcriptoma/genéticaRESUMEN
Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Histidina , Animales , Citidina Trifosfato , Histidina/genética , QueratinasRESUMEN
The cytoophidium, a subcellular structure composed of CTP synthase, can be observed during the division of Schizosaccharomyces pombe. Cytoophidium formation changes periodically with the cell cycle of yeast cells. Here, we find that histone chaperone Slm9 is required for the integrity of cytoophidia in fission yeast. When the slm9 gene is knocked out, we observe that morphological characteristics, the abundance of cytoophidia and the division of the yeast cells are significantly affected. Fragmented cytoophidia occur in slm9 mutant cells, a phenomenon rarely observed in wild-type cells. Our study reveals a potential link between a chromosomal regulatory factor and cytoophidium biogenesis.