Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxoplasma gondii establishes a lifelong chronic infection in humans and animals1. Host cell entry and egress are key steps in the lytic cycle of this obligate intracellular parasite, ensuring its survival and dissemination. Egress is temporally orchestrated, underpinned by the exocytosis of secretory organelles called micronemes. At any point during intracellular replication, deleterious environmental changes such as the loss of host cell integrity can trigger egress2 through the activation of the cyclic guanosine monophosphate-dependent protein kinase G3. Notably, even in the absence of extrinsic signals, the parasites egress from infected cells in a coordinated manner after five to six cycles of endodyogeny multiplication. Here we show that diacylglycerol kinase 2 is secreted into the parasitophorous vacuole, where it produces phosphatidic acid. Phosphatidic acid acts as an intrinsic signal that elicits natural egress upstream of an atypical guanylate cyclase (GC), which is uniquely conserved in alveolates4 and ciliates5, and composed of a P4-ATPase and two GC catalytic domains. Assembly of GC at the plasma membrane depends on two associated cofactors - the cell division control 50.1 and a unique GC organizer. This study reveals the existence of a signalling platform that responds to an intrinsic lipid mediator and extrinsic signals to control programmed and induced egress.
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PMID:Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform. 3094 49

This study sought novel ionizing radiation-response (IR-response) genes in Caenorhabditis elegans (C. elegans). C. elegans was divided into three groups and exposed to different high doses of IR: 0 gray (Gy), 200 Gy, and 400 Gy. Total RNA was extracted from each group and sequenced. When the transcriptomes were compared among these groups, many genes were shown to be differentially expressed, and these genes were significantly enriched in IR-related biological processes and pathways, including gene ontology (GO) terms related to cellular behaviours, cellular growth and purine metabolism and kyoto encyclopedia of genes and genomes (KEGG) pathways related to ATP binding, GTPase regulator activity, and RNA degradation. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that these genes displayed differential expression across the treatments. Further gene network analysis showed a cluster of novel gene families, such as the guanylate cyclase (GCY), Sm-like protein (LSM), diacylglycerol kinase (DGK), skp1-related protein (SKR), and glutathione S-transferase (GST) gene families which were upregulated. Thus, these genes likely play important roles in IR response. Meanwhile, some important genes that are well known to be involved in key signalling pathways, such as phosphoinositide-specific phospholipase C-3 (PLC-3), phosphatidylinositol 3-kinase age-1 (AGE-1), Raf homolog serine/threonine-protein kinase (LIN-45) and protein cbp-1 (CBP-1), also showed differential expression during IR response, suggesting that IR response might perturb these key signalling pathways. Our study revealed a series of novel IR-response genes in Caenorhabditis elegans that might act as regulators of IR response and represent promising markers of IR exposure.
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PMID:High-throughput transcriptome sequencing reveals extremely high doses of ionizing radiation-response genes in Caenorhabditis elegans. 3158 52