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Genomes and Genes | Joseph W LynchSummaryAffiliation: University of Queensland Country: Australia Publications
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Publications
Molecular structure and function of the glycine receptor chloride channelJoseph W Lynch
School of Biomedical Sciences, Univ of Queensland, Brisbane QLD 4072, Australia
Physiol Rev 84:1051-95. 2004....- Glycine receptors: a new therapeutic target in pain pathwaysJoseph W Lynch
School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
Curr Opin Investig Drugs 7:48-53. 2006..Future therapies aimed at specifically increasing current flux through alpha3-containing GlyRs may prove effective in providing analgesia... 
Subunit-specific potentiation of recombinant glycine receptors by NV-31, a bilobalide-derived compoundJoseph W Lynch
School of Biomedical Sciences and Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
Neurosci Lett 435:147-51. 2008..GlyRs are potential therapeutic targets for chronic anti-inflammatory pain and movement disorders. NV-31, as a positive modulator of these receptors, thus remains viable as a therapeutic candidate for these disorders...- Native glycine receptor subtypes and their physiological rolesJoseph W Lynch
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia
Neuropharmacology 56:303-9. 2009..Finally, agents that selectively potentiate different GlyR isoforms may be useful as therapeutic lead compounds for peripheral inflammatory pain and movement disorders such as spasticity... - Dihydropyridine inhibition of the glycine receptor: subunit selectivity and a molecular determinant of inhibitionXuebin Chen
School of Biomedical Sciences and Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
Neuropharmacology 56:318-27. 2009..The differential sensitivities of nifedipine and nicardipine for different GlyR isoforms suggest that DHPs may be a useful resource to screen as pharmacological tools for selectively inhibiting different synaptic GlyR isoforms... - A picrotoxin-specific conformational change in the glycine receptor M2-M3 loopRebecca Hawthorne
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 280:35836-43. 2005..We thus conclude that the picrotoxin-specific effects on the M2-M3 loop are mediated allosterically. This suggests that the M2-M3 loop responds differently to the occupation of different binding sites... 
Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domainStephan A Pless
Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 284:15847-56. 2009..These results provide an important step toward mapping the domains crucial for ligand discrimination in the ligand-binding domain of glycine receptors and possibly other Cys loop receptors...- Molecular pharmacology of the glycine receptor chloride channelTimothy I Webb
School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
Curr Pharm Des 13:2350-67. 2007..These issues need to be addressed before GlyR-specific therapeutics can be developed... - Tropisetron modulation of the glycine receptor: femtomolar potentiation and a molecular determinant of inhibitionZhe Yang
School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
J Neurochem 100:758-69. 2007..To our knowledge, tropisetron is the most exquisitely sensitive modulator yet identified for a cys-loop receptor... - A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor poreZhe Yang
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
J Neurochem 103:580-9. 2007.... - A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residueStephan A Pless
School of Biomedical Sciences and Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia
J Neurosci 28:10937-42. 2008..The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter... - Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunitsStephan A Pless
Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, Brisbane, Australia
J Neurochem 108:1585-94. 2009.... - A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonistsStephan A Pless
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
Mol Pharmacol 79:742-8. 2011..These data therefore show that similar agonists can have similar but not identical orientations and interactions in the binding pocket and provide a possible explanation for the lower potencies of β-alanine and taurine... - The M4 transmembrane segment contributes to agonist efficacy differences between alpha1 and alpha3 glycine receptorsXuebin Chen
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
Mol Membr Biol 26:321-32. 2009..This strong influence of M4 primary structure on partial agonist efficacy suggests that the relatively poorly conserved alpha3 GlyR M4 segment may be a promising domain to target in the search for alpha3 GlyR-specific modulators... - Function of hyperekplexia-causing α1R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signalling pathwayQiang Shan
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
Br J Pharmacol 165:2113-23. 2012..Such a strategy makes it possible to design an ideal drug, which only corrects the function of the mutant or modified protein without affecting the WT or naive protein... - Asymmetric contribution of alpha and beta subunits to the activation of alphabeta heteromeric glycine receptorsQiang Shan
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
J Neurochem 86:498-507. 2003..In conclusion, this study demonstrates that beta subunits contribute to the activation of the GlyR, but that their involvement in this process is significantly different to that of the alpha subunit... - Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptorQian Wang
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia
J Biol Chem 286:38814-24. 2011.... - Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channelTimothy Lynagh
Queensland Brain Institute, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
J Biol Chem 286:43913-24. 2011.... - Molecular determinants of ginkgolide binding in the glycine receptor poreRebecca Hawthorne
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
J Neurochem 98:395-407. 2006..This identified an interaction between the variable R2 position of the ginkgolides and the 2' residues of both alpha1 and beta subunits. These findings provide strong evidence for ginkgolides binding at the 2' pore-lining position... - Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacyStephan A Pless
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia
J Biol Chem 284:27370-6. 2009..Our results support the conclusion that a closed-flip conformation change, with a magnitude proportional to the agonist affinity increase from closed to flip states, occurs in the microenvironment of Ala-52... - GABAA receptors containing gamma1 subunits contribute to inhibitory transmission in the central amygdalaAbolghasem Esmaeili
The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
J Neurophysiol 101:341-9. 2009..These inputs arise from the intercalated cells masses, thought to be responsible for mediating extinction of conditioned fear, raising the possibility of new targets for the treatment of anxiety-related disorders... - Insights into the structural basis for zinc inhibition of the glycine receptorSimon T Nevin
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 278:28985-92. 2003..The binding of zinc at the interface between adjacent alpha1 subunits could restrict intersubunit movements, providing a feasible mechanism for the inhibition of channel activation by zinc... - Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptorNian Lin R Han
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 279:19559-65. 2004..We therefore conclude that the higher efficacy of glycine is due to an increased ability to stabilize a common activated configuration... - Molecular determinants of beta-carboline inhibition of the glycine receptorXuebin Chen
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Neurochem 110:1685-94. 2009..The information may also be relevant to understanding the mechanism beta-carboline of binding to GABA type A receptors where they are potent pharmacological probes... - β Subunit M2-M3 loop conformational changes are uncoupled from α1 β glycine receptor channel gating: implications for human hereditary hyperekplexiaQiang Shan
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia
PLoS ONE 6:e28105. 2011..Our study provides a possible explanation of why hereditary hyperekplexia-causing mutations that modify α1 β GlyR channel function are almost exclusively located in the α1 to the exclusion of the β subunit... - Ligand- and subunit-specific conformational changes in the ligand-binding domain and the TM2-TM3 linker of {alpha}1 {beta}2 {gamma}2 GABAA receptorsQian Wang
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 285:40373-86. 2010..This result implies unexpected conformational mobility in this crucial part of the gating machinery. Together, this information provides new insights into the activation mechanisms of Cys-loop receptors... - Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycineZhe Yang
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
Biochem Pharmacol 76:1014-23. 2008..We conclude that cannabinoid agonists may be useful as pharmacological tools for selectively inhibiting alpha2 and alpha3 GlyRs. Our results also establish GlyRs as potential novel targets for endogenous and exogenous cannabinoids... - Conformational variability of the glycine receptor M2 domain in response to activation by different agonistsStephan A Pless
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 282:36057-67. 2007..Thus, results from two separate labeled residues support the conclusion that the glycine receptor M2 domain responds with distinct conformational changes to activation by different agonists... - A comparison of glycine- and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domainQian Wang
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
Int J Biochem Cell Biol 44:335-40. 2012..This implies that conformational changes in these domains are important for activation. This result also provides a mechanism to explain how ivermectin potentiates glycine-induced channel activation... - Structure-activity analysis of ginkgolide binding in the glycine receptor poreJudith A Heads
School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
J Neurochem 105:1418-27. 2008..This property may be exploited to create improved pharmacological probes for discriminating among anionic Cys-loop receptor isoforms with 6' structural variations... - An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populationsTimothy Lynagh
Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, Brisbane QLD 4072, Australia
J Biol Chem 285:14890-7. 2010..As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity... - Comparative surface accessibility of a pore-lining threonine residue (T6') in the glycine and GABA(A) receptorsQiang Shan
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia
J Biol Chem 277:44845-53. 2002..The results also indicate that the GABA(A)R pore structure at the 6' level may vary between different expression systems... - Optimizing the expression of recombinant alphabetagamma GABAA receptors in HEK293 cells for high-throughput screeningDaniel Gilbert
Queensland Brain Institute, University of Queensland, Brisbane, Australia, School of Biomedical Sciences, University of Queensland, Brisbane, Australia
J Biomol Screen 14:86-91. 2009..The authors conclude that this method of expressing and screening recombinant GABA(A)Rs provides an effective means of discovering novel GABA(A)R modulators for use as therapeutic lead compounds and pharmacological probes... - A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptorsTimothy Lynagh
Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, Brisbane QLD, Australia
Int J Parasitol 40:1477-81. 2010..By providing a means of identifying ivermectin-sensitive receptors, this finding should help in characterising ivermectin-resistance mechanisms and identifying new anthelmintic targets... - Stoichiometry and subunit arrangement of α1β glycine receptors as determined by atomic force microscopyZhe Yang
Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
Biochemistry 51:5229-31. 2012..This permitted us to infer the number and relative locations of the respective subunits in functional pentamers. Our results indicate an invariant 2α1:3β stoichiometry with a β-α-β-α-β subunit arrangement... - A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABAA receptor chloride channelsWade Kruger
School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia
Neurosci Lett 380:340-5. 2005..The robustness, sensitivity and low cost of this assay render it suited for high-throughput screening of transiently expressed anionic ligand-gated channels... - Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2Florian M Gebhardt
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia
J Biol Chem 285:31313-24. 2010..This could allow glutamate to accumulate extracellularly and promote excitotoxicity... - Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family IrciniidaeWalter Balansa
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Bioorg Med Chem 18:2912-9. 2010..Such GlyR modulators have potential application as pharmacological tools, and as leads for the development of GlyR targeting therapeutics to treat chronic inflammatory pain, epilepsy, spasticity and hyperekplexia... - Closed-state cross-linking of adjacent beta1 subunits in alpha1beta1 GABAa receptors via introduced 6' cysteinesZhe Yang
School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia
J Biol Chem 282:16803-10. 2007..Our results identify a novel feature of GABA(A)R gating that may be important for understanding its activation mechanism... - Illuminating the structure and function of Cys-loop receptorsStephan A Pless
School of Biomedical Sciences and Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia
Clin Exp Pharmacol Physiol 35:1137-42. 2008..They have shed new light on the conformational mobility of both the ligand-binding and the transmembrane domain of Cys-loop receptors... - Mechanism of action of the insecticides, lindane and fipronil, on glycine receptor chloride channelsRobiul Islam
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
Br J Pharmacol 165:2707-20. 2012..We also investigated the mechanisms by which lindane and fipronil inhibit α1 glycine receptors... - Fluorescence-based high-throughput functional profiling of ligand-gated ion channels at the level of single cellsSahil Talwar
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
PLoS ONE 8:e58479. 2013.... - Effects of polyunsaturated fatty acids on voltage-gated K+ and Na+ channels in rat olfactory receptor neuronsBenchamaporn Seebungkert
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, 4072, Australia
Eur J Neurosci 16:2085-94. 2002..These observations suggest that polyunsaturated fatty acids have the potential to strongly influence the coding of odorant information by olfactory receptor neurons... - Multiplexed labeling of viable cells for high-throughput analysis of glycine receptor function using flow cytometryDaniel F Gilbert
Queensland Brain Institute, University of Queensland, Brisbane QLD 4072, Australia
Cytometry A 75:440-9. 2009..The present study demonstrates multiplexed labeling of live cells, to enable cell populations to be subject to further cell culture and experimentation, and compares the results with those obtained using live cell microscopy... - The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptorsLu Han
Queensland Brain Institute, The University of Queensland, Brisbane QLD 4072, Australia
ACS Chem Neurosci 4:248-54. 2013..We conclude that the α1 and α3 GlyR TM4 domains are orientated differently relative to their TM3 domains. This may underlie their differential ability to influence glycine efficacy... - Chimera construction using multiple-template-based sequential PCRsQiang Shan
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia
J Neurosci Methods 193:86-9. 2010..By introducing the "multiple-template" concept, this protocol only requires the use of two or three simple PCRs followed by general subcloning steps. Most importantly, the success rate is nearly 100%... - Ligand-gated channelsPeter H Barry
School of Medical Sciences at the University of New South Wales, Sydney, NSW 2052, Australia
IEEE Trans Nanobioscience 4:70-80. 2005..The superfamily will mainly be exemplified by the excitatory nicotinic acetylcholine receptor (nAChR) and the inhibitory glycine receptor (GlyR) channels...