Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drosophila peripheral nerves, similar structurally to the peripheral nerves of mammals, comprise a layer of axons and inner glia, surrounded by an outer perineurial glial layer. Although it is well established that intercellular communication occurs among cells within peripheral nerves, the signaling pathways used and the effects of this signaling on nerve structure and function remain incompletely understood. Here we demonstrate with genetic methods that the Drosophila peripheral nerve is a favorable system for the study of intercellular signaling. We show that growth of the perineurial glia is controlled by interactions among five genes: ine, which encodes a putative neurotransmitter transporter; eag, which encodes a potassium channel; push, which encodes a large, Zn(2+)-finger-containing protein; amn, which encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide; and NF1, the Drosophila ortholog of the human gene responsible for type 1 neurofibromatosis. In other Drosophila systems, push and NF1 are required for signaling pathways mediated by Amn or the pituitary adenylate cyclase activator peptide. Our results support a model in which the Amn neuropeptide, acting through Push and NF1, inhibits perineurial glial growth, whereas the substrate neurotransmitter of Ine promotes perineurial glial growth. Defective intercellular signaling within peripheral nerves might underlie the formation of neurofibromas, the hallmark of neurofibromatosis.
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PMID:Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways. 1151 34

The neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems.
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PMID:PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. 1624 93

Identifying modifiers of glioma risk in patients with type I neurofibromatosis (NF1) could help support personalized tumor surveillance, advance understanding of gliomagenesis, and potentially identify novel therapeutic targets. Here, we report genetic polymorphisms in the human adenylate cyclase gene adenylate cyclase 8 (ADCY8) that correlate with glioma risk in NF1 in a sex-specific manner, elevating risk in females while reducing risk in males. This finding extends earlier evidence of a role for cAMP in gliomagenesis based on results in a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP signaling might render males and females differentially sensitive to variation in cAMP levels. Using male and female Nf1 GEM, we found significant sex differences exist in cAMP regulation and in the growth-promoting effects of cAMP suppression. Overall, our results establish a sex-specific role for cAMP regulation in human gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in NF1.
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PMID:The cyclic AMP pathway is a sex-specific modifier of glioma risk in type I neurofibromatosis patients. 2538 Nov 54

Neurofibromatosis type I (NF1) is multisystemic disease characterized by pigmentary skin changes, increased susceptibility to tumor formation, neurological deficits and skeletal defects. The disease is a monogenic, autosomal dominant disorder, caused by the presence of mutations in the NF1 gene encoding neurofibromin - a multifunctional regulatory protein. The basic function of neurofibromin protein is modulation of the RAS protein activity necessary for regulation of cell proliferation and differentiation by the RAS/MAPK and RAS/PI3K/AKT signal transduction pathways. In addition, neurofibromin is a regulator of adenylate cyclase activity and therefore may interfere with signaling by the cAMP/protein kinase A pathway that regulates cell cycle progression or learning and memory formation processes. Neurofibromin also interacts with many other proteins that are engaged in intracellular transport (tubulin, kinesin), actin cytoskeleton rearrangements (LIMK2, Rho and Rac) or morphogenesis of neural cells (syndecans, CRMP proteins). The activity of neurofibromin is strictly regulated by the expression of different NF1 mRNA isoforms depending on tissue type or period in organism development, the protein localization, posttranslational modifications (phosphorylation, ubiquitination) or interactions with other proteins (e.g. 14-3-3). The fact that neurofibromin is engaged in many cellular processes has significant consequences when the proper protein functioning is impaired due to decreased protein level or activity. It affects the normal cell function and results in disturbances of organism development that lead to the occurrence of clinical signs specific for NF1. In the article, the basic neurofibromin functions are presented in the context of the molecular pathogenesis of NF1.
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PMID:[Neurofibromin - protein structure and cellular functions in the context of neurofibromatosis type I pathogenesis]. 2667 24