Effects of Aromatic Substituents on the Photocleavage of 1-Acyl-7-nitroindolines

Papageorgiou, George; Corrie, John E. T.

doi:10.1016/s0040-4020(00)00745-6

Cited by 112 publications

(96 citation statements)

References 12 publications

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“…Both compounds are suitable for studies on NMDA receptors (16,17), with MNI-caged amino acids being characterized by higher photorelease efficiency compared with the NI-based precursors (18). MNI-caged glutamate, therefore, was used preferentially with low affinity mutant receptors.…”

Section: Methodsmentioning

confidence: 99%

Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-d-aspartate Receptor Activation

Maier

Schemm

Grewer

et al. 2007

Journal of Biological Chemistry

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Ionotropic glutamate receptors (iGluRs)4 are the major mediators of excitatory neurotransmission in the brain and play important roles both in neuronal development and synaptic function (1). They are tetrameric protein complexes (2, 3) in which each subunit is composed of (i) an extracellular aminoterminal domain, (ii) a ligand binding domain (LBD), sharing sequence homology to bacterial periplasmic binding proteins, (iii) a membrane-associated domain with the transmembrane helices M1-M4 that forms the ion pore, and (iv) an intracellular carboxyl-terminal domain (4).The family of iGluRs is divided into the subclasses of AMPA, kainate, and NMDA receptors that differ, among other things, in their ligand specificities (1). Despite the pharmacological differences, crystal structures have been obtained for LBDs of subunits from all three subclasses of iGluRs (5-9) and have revealed a conserved clam shell-like architecture of two lobes (D1 and D2) around a central cleft that harbors the ligand binding site. Lobe D1 is formed from residues preceding the first transmembrane domain (M1) and the C-terminal residues of the extracellular loop between transmembrane domains 3 and 4, whereas the N-terminal part of this loop forms lobe D2.LBD structures in complex with different ligands (10 -12) have shed light on the molecular mechanism of ligand binding and, in the absence of structural information on the transmembrane domain, have led to the formulation of hypotheses on how agonist binding may be coupled to channel gating. Agonists differ from antagonists in that they promote closure of the LBD clam shell through rotation of lobe D2 toward D1. In a largely mechanical model of receptor activation (11), this motion is thought to generate conformational strain within the tetrameric receptor complex that transduces to the membrane regions and, eventually, causes channel opening. Several studies in AMPA and kainate iGluRs (6, 7, 11) relating structure to agonist efficacy show that the degree of domain closure induced by different agonists correlates with their functional activity. Interestingly, there is evidence that the glycine binding domain of the NR1 subunit of the NMDA receptor does not exhibit a similar correlation between domain closure and agonist efficacy (8,12). Recent structure-function data show that engineering sterical restrictions within the glutamate-binding pocket of the NR2B subunit of the NMDA receptor is correlated to the degree of agonist efficacy (13), implicating that the action of glutamate and glycine on the NR2 and NR1 subunits, respectively, may induce different structural mechanisms underlying agonist efficacy.However, although crystallographic data have uncovered the difference between agonist-and antagonist-bound LBD struc-

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Section: Methodsmentioning

confidence: 99%

Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-d-aspartate Receptor Activation

Maier

Schemm

Grewer

et al. 2007

Journal of Biological Chemistry

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“…Abstr. 26, 425.13, 2000) using a synthetic sequence similar to that already described 46 . (Significant modifications are fully detailed in the Supplementary Methods, available on the supplementary information page of Nature Neuroscience online.)…”

Section: Two-photon Excitation Of a Caged-glutamate Compoundmentioning

confidence: 99%

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/ spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.Most excitatory synaptic transmission in the mammalian central nervous system relies on glutamate as a neurotransmitter, and postsynaptic glutamate receptors are central in both the acquisition and maintenance of memory 1, 2 . Substantial biochemical evidence indicates that glutamate receptors in postsynaptic densities (PSDs) are regulated by various protein machineries that link the receptors to the cytoskeleton 3,4,5 and that control the insertion [6][7][8][9][10] and phosphorylation of the receptors 11,12 . Individual dendritic spines have been thought to act as functional compartments of glutamate receptor expression, given that they are physically and thus metabolically separated from the body of the dendrite by the narrow spine neck [13][14][15][16] . Indeed, the Hebbian principle of learning as well as most theories of neuronal networks assume that the strength of synaptic connections is subject to independent control 17 . Moreover, spine geometry has been proposed to be a key determinant of synaptic function and memory in the brain 13, 14, 18-22 . Correspondence to: Haruo Kasai. These various hypotheses have not been tested experimentally, however, because it is not possible to systematically investigate postsynaptic glutamate sensitivities at the level of the individual spine by classical electrophysiological approaches 16,23 . Also, the number of functional AMPA-sensitive glutamate receptors in individual spines has not been estimated directly. Two-photon excitation of caged-glutamate compounds may overcome these difficulties 24 as a result of the inherent three-dimensional resolution of neurotransmitter application associated with this technique. However, caged-glutamate compounds with a cross-section for two-photon absorption, a rate of photolysis, and a stability in aqueous solution sufficient for such studies have not previously been described [25][26][27] . NIH Public AccessWe developed a caged-glutamate compound and microscopic system for two-photon excitation that allowed systematic investigation of functional glutamate receptors at the level of the individual synapse. Our experiment...

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“…The quantum yields Q P are 0.043 for the NI-cage (Papageorgiou et al 1999) and 0.085 for the MNI-cage (Papageorgiou and Corrie 2000).…”

Section: Laser Flash Photolysismentioning

confidence: 97%

“…The extinction coefficients at ϭ 347 nm are (in M Ϫ1 cm Ϫ1 ): for the NI-cage, E CG ϭ 2720 (Papageorgiou et al 1999); for the MNI-cage, E CG ϭ 4330 (Papageorgiou and Corrie 2000); for the photoproducts, E N ϭ 1400 and 2660, respectively (J.E.T. Corrie, personal communication).…”

Section: Laser Flash Photolysismentioning

confidence: 99%

Flash Photolysis Reveals a Diversity of Ionotropic Glutamate Receptors on the Mitral Cell Somatodendritic Membrane

Lowe

2003

Journal of Neurophysiology

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Lowe, Graeme. Flash photolysis reveals a diversity of ionotropic glutamate receptors on the mitral cell somatodendritic membrane. J Neurophysiol 90: 1737-1746, 2003. First published April 30, 2003 10.1152/jn.00180.2003. It is widely held that the soma and basal dendrites of olfactory bulb mitral cells receive exclusively inhibitory synaptic input from local interneurons. However, the mitral somatodendritic membrane exhibits immunoreactivity for a variety of glutamate receptors, and blocking GABA receptors unmasks mitral cell self-excitation. This excitation is proposed to be mediated either by diffuse spillover of the mitral cells' own released glutamate, or by punctate transmission from glutamate-releasing granule cells. This study examined the pharmacology and kinetics of glutamate sensitivity of mitral cells by flash photolysis of nitroindoline caged glutamates, which facilitate reliable activation of receptors in the synaptic cleft. Wide-field laser uncaging (3.5-ms flash) of approximately 0.5-1 mM glutamate onto the soma activated large currents with fast (3.4-ms rise, 7.5-ms decay) and slow (64-ms rise, Ͼ10-s decay) components. In 100 M APV, slow currents were reduced to 53% of control (257-ms rise, 2-s decay), displayed outward rectification in 1.3 mM Mg 2ϩ , and blocked by 15 M 5,7-dichlorokynurenate. Responses to Շ100 M glutamate were fully antagonized by 100 M APV, consistent with competitive inhibition at high-affinity NMDA receptors. An APV-resistant NMDA receptor was not observed, refuting the punctate transmission model. Fast currents were blocked by 10 M NBQX, boosted 3.28-fold by 100 M cyclothiazide, and resolved into AMPA (40%) and kainate (60%) receptor components by 100 M SYM2206. The results suggest that self-excitation depends on AMPA, kainite, and conventional NMDA autoreceptors on the mitral cell.

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Effects of Aromatic Substituents on the Photocleavage of 1-Acyl-7-nitroindolines

Cited by 112 publications

References 12 publications

Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-d-aspartate Receptor Activation

Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-d-aspartate Receptor Activation

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Flash Photolysis Reveals a Diversity of Ionotropic Glutamate Receptors on the Mitral Cell Somatodendritic Membrane

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