Protein Phosphatase 1 regulates atypical chromosome segregation and cell polarity during mitotic and meiotic division in Plasmodium sexual stages
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ABSTRACT:
PROVIDER: PRJNA689429 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13347513_1.fastq.gz | Fastqsanger.gz | |||
| SRR13347513_2.fastq.gz | Fastqsanger.gz | |||
| SRR13347514_1.fastq.gz | Fastqsanger.gz | |||
| SRR13347514_2.fastq.gz | Fastqsanger.gz | |||
| SRR13347515_1.fastq.gz | Fastqsanger.gz |
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Project description:PP1 is a conserved serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25, in model eukaryotes. However, the malaria parasite, Plasmodium spp. lacks the CDC14 and CDC25 genes. The proliferative stages of the parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, with three rounds of DNA synthesis, successive spindle formation with clustered kinetochore, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved these unusual processes. Using real-time live-cell imaging, conditional gene knockdown, RNAseq and proteomic approaches, we show that Plasmodium PP1 is involved in both chromosome segregation during mitotic exit, and establishment of cell polarity during these sexual stages, suggesting that PP1 inhibitors may block parasite transmission.
2021-07-08 | GSE164175 | GEO
Project description:PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show that Plasmodium PP1 is involved in both chromosome segregation during mitotic exit, and potentially establishment of cell polarity during zygote development in the mosquito midgut, suggesting that chemical inhibitors of PP1 may be explored for blocking parasite transmission
2021-09-10 | PXD023571 | Pride
Project description:PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell and ultrastructural imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show that Plasmodium PP1 is implicated in both mitotic exit and, potentially, establishing cell polarity during zygote development in the mosquito midgut, suggesting that small molecule inhibitors of PP1 should be explored for blocking parasite transmission.
| S-EPMC8213788 | biostudies-literature
Project description:Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP unique region (LUR) of these proteins is essential for ABP function, and includes a highly conserved Leucine Reach Repeat (LRR) domain. Here we study how the LRR domain of Scribble maintains ABP. We show that its concave surface participates in three types of mutually exclusive interactions 1. homodimerization serving as an auto-inhibitory mechanism, 2. interactions with a diverse set of polarity proteins, such as Llgl1, Llgl2, EPB41L2 and EPB41L5, which produce distinct multiprotein complexes, and 3. a direct interaction with the protein phosphatase, PP1, which forms a dimeric LRR domain-PP1 complex. Our results suggest that the latter complex maintains PP1 in the basolateral cell cortex in close proximity to PP1 targets. Such organization generates a dynamic network where PP1 could be immediately dispatched from the Scribble-PP1 complex to particular protein ligands. This mechanism for controlling dephosphorylation kinetics of phosphorylated proteins could be universal for all members of the LAP protein family, which includes Erbin, Lano, and the neuron-specific protein, Densin-180.
2021-11-03 | PXD028919 | Pride
Project description:The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC – PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz – are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.
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Project description:The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC – PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz – are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.
2024-04-21 | GSE263979 | GEO
Project description:Liver Cancer Evolution - Lesion segregation
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Project description:Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.
2021-09-25 | GSE135306 | GEO
Project description:Genome/chromosome organization is highly ordered and controls nuclear events. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosome organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. Genome-wide distributions of condensin and Pol III factors in fission yeast.
2015-08-12 | E-GEOD-60273 | biostudies-arrayexpress
Project description:Cell polarity is crucial for the maintenance of epithelial cell function and its loss may have an im-portant role in the development and progression of cancer. We here show that overexpression and cytoplasmic enrichment of the baso-lateral polarity complex protein Scribble (Scrib) correlates with poor prognosis of hepatocellular cancer (HCC) patients. Expression of the cytoplasmic ScribP305L in hepatocellular cells induces epithelial to mesenchymal transition (EMT) and supports HCC cell invasion in comparison to cells expressing membrane-localized ScribWT. ScribP305L induces AKT signalling through destabilization of the phosphatases phosphatase and tensin homolog (PTEN) and PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1). Moreover, cytoplasmic ScribP305L stimulates the expression of secreted protein acidic and cysteine rich (SPARC) de-pending on the AP1 constituents ATF2 and JunB, which drives HCC cell invasiveness. In vivo, combined hydrodynamic delivery of ScribP305L but not ScribWT and c-MYC initiates tumour for-mation in hepatocytes and cytoplasmic Scrib correlates with AKT phosphorylation, and AP1 ex-pression in human HCC tissues. Together, overexpression and mislocalization of Scrib represents an early event involved in the initiation and progression of liver cancer.
2017-11-30 | GSE93742 | GEO