Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The G(s)-proteins G(salpha-short) (G(salphaS)) and G(salpha-long) (G(salphaL)), and the olfactory G(s) protein (G(alphaolf)) mediate activation of adenylyl cyclase by the beta(2)-adrenoceptor (beta(2)AR). Early studies showed that the purine nucleotides GTP, ITP, and XTP differentially support receptor-mediated adenylyl cyclase activation in various native membrane systems, but those findings have remained unexplained thus far. We systematically analyzed the effects of GTP, ITP, and XTP on the coupling of the beta(2)AR to G(salphaS), G(salphaL), and G(alphaolf), respectively, using fusion proteins expressed in Sf9 insect cells. Fusion proteins ensure defined receptor/G-protein stoichiometry and efficient coupling. At all three fusion proteins, GTP, ITP, and XTP exhibited unique profiles with respect to their potency and efficacy at disrupting high-affinity agonist binding and supporting adenylyl cyclase activation by partial and full agonists. Our data can be interpreted in two ways: (i) GTP, ITP, and XTP may stabilize different active conformations in various G(s)-proteins, or (ii) GTP, ITP, and XTP may differ from one another in the kinetics of interaction with various G(s)-proteins. Regardless of which of the two explanations is correct, our present data demonstrate that GTP, ITP, and XTP are highly efficient regulators of signal transduction mediated through a specific G-protein. Also discussed is the possibility that G-protein activation by ITP and XTP may be of relevance in Lesch-Nyhan syndrome, a defect of the purine salvage pathway associated with abnormalities in various neurotransmitter systems.
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PMID:Distinct interactions of G(salpha-long), G(salpha-short), and G(alphaolf) with GTP, ITP, and XTP. 1216 77

Calsyntenins/alcadeins are type I transmembrane proteins with two extracellular cadherin domains highly expressed in mammalian brain. They form a tripartite complex with X11/X11L and APP (amyloid precursor protein) and are proteolytically processed in a similar fashion to APP. Although a genetic association of calsyntenin-2 with human memory performance has recently been reported, physiological roles and molecular functions of the protein in the nervous system are poorly understood. Here, we show that CASY-1, the Caenorhabditis elegans ortholog of calsyntenins/alcadeins, is essential for multiple types of learning. Through a genetic screen, we found that casy-1 mutants show defects in salt chemotaxis learning. casy-1 mutants also show defects in temperature learning, olfactory adaptation, and integration of two sensory signals. casy-1 is widely expressed in the nervous system. Expression of casy-1 in a single sensory neuron and at the postdevelopmental stage is sufficient for its function in salt chemotaxis learning. The fluorescent protein-tagged ectodomain of CASY-1 is released from neurons. Moreover, functional domain analyses revealed that both cytoplasmic and transmembrane domains of this protein are dispensable, whereas the ectodomain, which contains the LG/LNS-like domain, is critically required for learning. These results suggest that learning is modulated by the released ectodomain of CASY-1.
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PMID:CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans. 1838 21

Information on systematic analysis of olfactory memory-related proteins is poor. In this study, the odor discrimination task to investigate olfactory recognition memory of adult male C57BL/6J mice was used. Subsequently, olfactory bulbs (OBs) were taken, proteins extracted, and run on two-dimensional gel electrophoresis with in-gel-protein digestion, followed by mass spectrometry and quantification of differentially expressed proteins. Dual specificity mitogen-activated protein kinase kinase 1 (MEK1), dihydropyrimidinase-related protein 1 (DRP1), and fascin are related with Lemon odor memory. Microtubule-associated protein RP/EB family member 3 is related to Rose odor memory. Hypoxanthine-guanine phosphoribosyltransferase is related with both Lemon and Rose odors memory. MEK1 and DRP1 levels were increased, while microtubule-associated protein RP/EB family member 3, fascin and hypoxanthine-guanine phosphoribosyltransferase levels were decreased during olfactory memory. In summary, neurogenesis, signal transduction, cytoskeleton, and nucleotide metabolism are involved in olfactory memory formation and storage of C57BL/6J mice.
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PMID:Olfactory bulb proteins linked to olfactory memory in C57BL/6J mice. 2022 35

Earlier, we showed that micro RNA-132 (miR-132) regulate the immediate early genes (IEGs) in the olfactory bulb (OB) of fruit bat Cynopterus sphinx during olfactory learning. This study was designed to examine whether the miR-132 regulate other proteins in OB during olfactory learning. To test this, miR-132 anti-sense oligodeoxynucleotide (AS-ODN) was delivered to the OB and then trained to novel odor. The 2-dimensional gel electrophoresis analysis showed that inhibition of miR-132 altered olfactory training induced expression of 321 proteins. Further, liquid chromatography-mass spectrometry (LC-MS/MS) analysis reveals the identity of differently expressed proteins such as phosphoribosyl transferase domain containing protein (PRTFDC 1), Sorting nexin-8 (SNX8), Creatine kinase B-type (CKB) and Annexin A11 (ANX A11). Among them PRTFDC 1 showing 189 matching peptides with highest sequence coverage (67.0%) and protein-protein interaction analysis showed that PRTFDC 1 is a homolog of hypoxanthine phosphoribosyltransferase-1 (HPRT-1). Subsequent immunohistochemical analysis (IHC) showed that inhibition of miR-132 down-regulated HPRT expression in OB of C. sphinx. In addition, western blot analysis depicts that HPRT, serotonin transporter (SERT), N-methyl-d-asparate (NMDA) receptors (2A,B) were down-regulated, but not altered in OB of non-sense oligodeoxynucleotide (NS-ODN) infused groups. These analyses suggest that miR-132 regulates the process of olfactory learning and memory formation through SERT and NMDA receptors signalling, which is possibly associated with the PRTFDC1-HPRT interaction.
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PMID:MiR-132 regulated olfactory bulb proteins linked to olfactory learning in greater short-nosed fruit bat Cynopterus sphinx. 2985 84