Transcriptome profile of Haemaphysalis longicornis (Acari: Ixodidae) exposed to C. citratus essential oil and citronellal
Ontology highlight
ABSTRACT:
ORGANISM(S): Haemaphysalis longicornis
PROVIDER: GSE176275 | GEO | 2021/06/08
REPOSITORIES: GEO
Similar Datasets
Project description:In malaria parasites, all cGMP-dependent signalling is mediated through a single cGMP-dependent protein kinase (PKG). A major function of PKG is to control calcium signals essential for the parasite to exit red blood cells or for transmission to the mosquito vector. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we identify a tightly-associated PKG partner protein in Plasmodium falciparum asexual blood stages. Named ICM1, the partner is a polytopic membrane protein with homology to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis
2021-02-10 | PXD020447 | Pride
Project description:In malaria parasites, all cGMP-dependent signalling is mediated through a single cGMP-dependent protein kinase (PKG). A major function of PKG is to control calcium signals essential for the parasite to exit red blood cells or for transmission to the mosquito vector. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we identify a tightly-associated PKG partner protein in both Plasmodium falciparum asexual blood stages and P. berghei gametocytes. Named ICM1, the partner is a polytopic membrane protein with homology to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent upon PKG activity. Stage-specific depletion of ICM1 in P. berghei blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation, whilst conditional disruption of P. falciparum ICM1 results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Our findings provide new insights into the atypical calcium homeostasis in malaria parasites essential for pathology and disease transmission.
2021-02-10 | PXD020381 | Pride
Project description:In malaria parasites, cGMP signalling is mediated by a single cGMP-dependent protein kinase (PKG). One of the major functions of PKG is to control calcium signals essential for the parasite to exit red blood cells or for the transmission of the gametocyte stages to the mosquito. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we use pull-down approaches to identify a PKG partner protein in both Plasmodium falciparum schizonts and P. berghei gametocytes. This partner, named ICM1, is a polytopic membrane protein with homologies to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent on PKG activity. Conditional disruption of the P. falciparum ICM1 gene results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Stage-specific depletion of ICM1 in P. berghei gametocytes blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation. These results provide us with new insights into the atypical calcium homeostasis in malaria parasites
2021-01-25 | PXD020189 | Pride
Project description:In malaria parasites, cGMP signalling is mediated by a single cGMP-dependent protein kinase (PKG) . One of the major functions of PKG is to control calcium signals essential for the parasite to exit red blood cells or for the transmission of the gametocyte stages to the mosquito . However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we use pull-down approaches to identify a PKG partner protein in both Plasmodium falciparum schizonts and P. berghei gametocytes. This partner, named ICM1, is a polytopic membrane protein with homologies to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent on PKG activity. Conditional disruption of the P. falciparum ICM1 gene results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Stage-specific depletion of ICM1 in P. berghei gametocytes blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation. These results provide us with new insights into the atypical calcium homeostasis in malaria parasites.
2021-01-25 | PXD020210 | Pride
Project description:Through transcriptomic profiling, we compared differentially expressed genes between WT and pkg mutant treated with Br-cGMP, we found that PKG as primary receptor mediated cGMP signaling in rice.
2020-08-24 | GSE119028 | GEO
Project description:The aberrant activation of the ERG oncogenic pathway due to TMPRSS2-ERG gene fusions is the major driver of prostate cancer initiation and progression. We identified the alpha1 and beta1 subunits of soluble guanylyl cyclase (GUCY1A1, GUCY1B1) as major ERG-regulated genes in prostate cancer cells. Soluble guanylyl cyclase (sGC) is the major mediator of nitric oxide signaling in cells that, upon nitric oxide binding, catalyzes the synthesis of cGMP and subsequently activates PKG. We showed in ERG-positive PCa cells (VCaP) that cGMP synthesis was significantly elevated by ERG, leading to increased PKG activity and cell proliferation. To further understand the functions of sGC-cGMP pathway in prostate cancer cells, we performed RNA-seq analyses in VCaP cells to identify genes that are regulated by sGC.
2018-05-22 | GSE114738 | GEO
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development
2024-06-24 | PXD048979 | Pride
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development.
2024-06-24 | PXD049017 | Pride
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development.
2024-06-24 | PXD049083 | Pride
Project description:Toxoplasma gondii encodes three Protein Kinase A catalytic (PKAc1-3) and one regulatory (PKAr) subunits to integrate cAMP-dependent signals. Here, we show that inactive PKAc1 is maintained at the parasite pellicle by interacting with dually acylated PKAr. Either a conditional knockdown of PKAr or the overexpression of PKAc1 results in a block in parasite division. In contrast, conditional expression of a dominant negative PKAr isoform unable to bind cAMP, triggers premature egress of parasites from infected cells. This untimely egress critically depends on parasite density and host cell acidification. A comparative phosphoproteome analysis reveals that PKA genetic inhibition significantly changed the phosphorylation profile of a putative cGMP-phosphodiesterase, PDE2. Consistently, the phenotype of PKA genetic inhibition is alleviated by chemical inhibition of the cGMP-dependent protein kinase G (PKG). A phosphodiesterase inhibitor is able to circumvent egress repression by PKA or pH neutralisation, indicating that environmental acidification and PKA signalling act as balancing regulators of cGMP degradation to control PKG-mediated egress. Collectively, these results reveal a cross-talk between PKA and PKG pathways to govern egress in T. gondii.
2017-10-12 | PXD006045 | Pride