Search bioRxiv⌕ Search

Biology subjects

Dou, K.

Publications and source records attributed to Dou, K..

4 recordsLinked to original sources

Cytoskeleton Regulates Cytoophidium Dynamics in Drosophila Ovaries

Cytoophidia are filamentous structures composed of CTP synthase (CTPS) and were initially discovered in ovarian cells of Drosophila. As a highly conserved membraneless organelle present across all three domains of life, cytoophidia display dynamic behaviors that are crucial for cellular homeostasis and function. Previous research has shown that cytoophidia are actively transported from nurse cells to oocytes, implicating their potential role in Drosophila oogenesis. Nevertheless, the molecular and cellular mechanisms governing cytoophidium dynamics remain largely unclear. In this study, we employ live-cell imaging to systematically characterize the spatiotemporal dynamics of cytoophidia and to explore the underlying regulatory mechanisms. Our findings demonstrate that cytoophidium dynamics are dependent on the cytoskeletal components-- microtubules, microfilaments (actin filaments), and myosin II. Notably, disruption of either microtubules or microfilaments resulted in the disassembly or depolymerization of large cytoophidia (macro-cytoophidia), highlighting an essential role of the cytoskeleton in maintaining cytoophidium integrity and assembly. Together, these results indicate that microtubules, microfilaments, and myosin II play pivotal roles in regulating cytoophidium dynamics. This study provides new insights into the mechanisms underlying cytoophidium transport and assembly, and lays a foundation for further investigation of their functional significance in Drosophila oogenesis.

cell biology↗

Epigenetic reprogramming induced by Acetyl-CoA and SAM depletion is an evolutionarily-ancient path to malignant growth

Despite the vast diversity of life forms and living histories, it appears that all branches of Metazoa face the challenge of tumor growth. Contrary to human tumors, which take years to form, tumors in short-living species can arise within days without accumulating multiple mutations, raising the question whether the paths to tumorigenesis in diverse species have any commonalities. In a fly tumor model caused by loss of cell polarity genes, we first identified the rise of a glycolytic cell population over time, resembling the Wartburg effect observed in human tumors. We further identified two key metabolic changes in these fly tumors. First, a systemic depletion of acetyl-CoA leads to a reduction in histone acetylation levels and stochastic silencing of actively-transcribed genes. Second, defects in the methionine cycle cause a systemic depletion of S-Adenosyl methionine, which further reduces histone methylation levels and causes stochastic activation of transposons. Perturbation of the methionine metabolic process strongly inhibits tumor growth. Finally, to understand the evolutionary origin of tumorigenesis, we performed comparative studies of fly and human tumors, and identified human tumors that exhibit metabolic signatures similar to those of fly tumors. We found that human tumors with high metabolic similarity to fly tumors have a lower mutational load, younger patient age, and lower DNA methylation levels. This study suggests that tumorigenesis processes have a deep evolutionary origin and highlights that depletion of key metabolites is an evolutionarily-ancient driving force for tumorigenesis.

developmental biology↗

dP75 safeguards oogenesis by preventing H3K9me2 spreading

Serving as a host factor for HIV integration, LEDGF/p75 has been under extensive study as a potential target for therapy. However, as a highly conserved protein, its physiological function remains to be thoroughly elucidated. Here we characterize the molecular function of dP75, the Drosophila homolog of p75, during oogenesis. dP75 binds to transcriptionally active chromatin with its PWWP domain. The C-terminus IBD domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo. Together with Jil-1, dP75 prevents the spreading of the heterochromatin mark-H3K9me2-onto genes required for oogenesis and piRNA production. Without dP75, ectopically silencing of these genes disrupts oogenesis, activates transposons, and causes animal sterility. We propose that dP75, the homolog of an HIV host factor in Drosophila, partners with Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.

developmental biology↗

A novel polyphasic identification system for genus Trichoderma

As the rapid-changing in Trichoderma taxonomy, an efficient identification of Trichoderma species is an urgent issue for Trichoderma-based research. In this study, based on the current taxonomy of Trichoderma, we constructed curated databases including 338 ITS sequences, 435 TEF1 sequences, 415 RPB2 sequences and 28 phenotypic characters. In addition, a polyphasic identification system (PIST) was developed. Within PIST, the resolution ability of molecular and phenotype characters could be combined for species identification in a step-by-step way. Compared with other identification systems, the involved Trichoderma species were extended from 88 to 252 species and 175 from 188 tested Trichoderma species could be identified within PIST. In most tested cases, three nucleotide markers and phenotypic characters showed improved identification performance. The TEF1 sequences have superior resolution than other characters.\n\nImportanceThe genus Trichoderma is important to human society with a wide application in industry, agriculture and environment bio-remediation. Thus, a quick and accurate identification of Trichoderma spp. is paramount since it is usually the first step to conduct a Trichoderma-based scientific research and is an obstruction especially for those researchers as nematologist, chemists, nutritionist and the like, lacking of taxonomic knowledge of fungi.

microbiology↗