scholarly journals Cellular Sequences in Pestivirus Genomes Encoding Gamma-Aminobutyric Acid (A) Receptor-Associated Protein and Golgi-Associated ATPase Enhancer of 16 Kilodaltons

2002 ◽  
Vol 76 (24) ◽  
pp. 13069-13076 ◽  
Author(s):  
Paul Becher ◽  
Heinz-Jürgen Thiel ◽  
Margaret Collins ◽  
Joe Brownlie ◽  
Michaela Orlich
Keyword(s):  
Nonstructural Protein ◽  
Cellular Protein ◽  
Genomic Region ◽  
Aminobutyric Acid ◽  
Covalent Attachment ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Receptor Associated Protein ◽  
Diarrhea Virus ◽  
Viral Sequences

ABSTRACT The presence of cellular protein coding sequences within viral RNA genomes is a unique and particularly interesting feature of cytopathogenic (cp) pestiviruses. Here we report the identification and characterization of two novel cellular sequences in the genomes of cp bovine viral diarrhea virus (BVDV) strains. In BVDV strain CP X604, we detected a duplication of the genomic region encoding NS3, NS4A, and part of NS4B, together with an insertion of sequences that code for cellular gamma-aminobutyric acid (A) receptor-associated protein [GABA(A)-RAP]. Transient-expression studies showed that the GABA(A)-RAP sequence leads to additional processing of the viral polyprotein and thereby to the expression of nonstructural protein NS3. Transfection of bovine cells with RNA transcribed from an infectious cDNA clone revealed that the GABA(A)-RAP-encoding insertion together with the duplicated viral sequences constitutes the genetic basis for the cytopathogenicity of strain CP X604. Surprisingly, molecular analysis of another cp BVDV strain (CP 721) resulted in the identification of a cellular Golgi-associated ATPase enhancer of 16 kDa (GATE-16)-encoding insertion together with duplicated viral sequences. To our knowledge, the genomes of CP X604 and CP 721 are the first viral RNAs found with cellular sequences encoding GABA(A)-RAP and GATE-16, respectively. Interestingly, the two cellular proteins belong to a family of eukaryotic proteins involved in various intracellular trafficking processes. Processing after the C-terminal glycine residue of GABA(A)-RAP and GATE-16 by cellular proteases is essential for covalent attachment to target molecules. Accordingly, it can be assumed that these cellular proteases also recognize the cleavage sites in the context of the respective viral polyproteins and thereby lead to the generation of NS3, the marker protein of cp BVDV.

Gamma-aminobutyric acid (GABA): a para- and/or autocrine hormone in the pituitary

2001 ◽  
Vol 15 (6) ◽  
pp. 1089-1091 ◽  
Author(s):  
ARTUR MAYERHOFER ◽  
BARBARA HÖHNE-ZELL ◽  
KATIA GAMEL-DIDELON ◽  
HEIKE JUNG ◽  
PETER REDECKER ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A

scholarly journals Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52

2021 ◽  
Vol 7 (33) ◽  
pp. eabi6582
Author(s):  
Tao Fu ◽  
Mingfang Zhang ◽  
Zixuan Zhou ◽  
Ping Wu ◽  
Chao Peng ◽  
...  
Keyword(s):  
Protein Complex ◽  
Coiled Coil ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Related Protein ◽  
Binding Region ◽  
Receptor Associated Protein ◽  
Selective Autophagy ◽  
Specific Association ◽  
Molecular Bases

The recruitment of Unc-51-like kinase and TANK-binding kinase 1 complexes is essential for Nuclear dot protein 52-mediated selective autophagy and relies on the specific association of NDP52, RB1-inducible coiled-coil protein 1, and Nak-associated protein 1 (5-azacytidine-induced protein 2, AZI2). However, the underlying molecular mechanism remains elusive. Here, we find that except for the NDP52 SKIP carboxyl homology (SKICH)/RB1CC1 coiled-coil interaction, the LC3-interacting region of NDP52 can directly interact with the RB1CC1 Claw domain, as that of NAP1 FIP200-binding region (FIR). The determined crystal structures of NDP52 SKICH/RB1CC1 complex, NAP1 FIR/RB1CC1 complex, and the related NAP1 FIR/Gamma-aminobutyric acid receptor-associated protein complex not only elucidate the molecular bases underpinning the interactions of RB1CC1 with NDP52 and NAP1 but also reveal that RB1CC1 Claw and Autophagy-related protein 8 family proteins are competitive in binding to NAP1 and NDP52. Overall, our findings provide mechanistic insights into the interactions of NDP52, NAP1 with RB1CC1 and ATG8 family proteins.

scholarly journals Role of gamma aminobutyric acid A receptor associated protein (GABARAP) in the podocytes of GABARAP Tg mice

2011 ◽  
Vol 57 (5) ◽  
pp. 488-493
Author(s):  
MIYUKI TAKAGI ◽  
KATSUHIKO ASANUMA ◽  
ISEI TANIDA ◽  
YASUHIKO TOMINO
Keyword(s):  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Receptor Associated Protein

The pharmacology of gamma-aminobutyric acid and acetylcholine receptors at the echinoderm neuromuscular junction

2001 ◽  
Vol 204 (5) ◽  
pp. 887-896 ◽  
Author(s):  
C.L. Devlin
Keyword(s):  
Neuromuscular Junction ◽  
Gaba Receptors ◽  
Muscle Fibers ◽  
The Body ◽  
Aminobutyric Acid ◽  
Receptor Subtypes ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Rhythmic Contractions ◽  
Ach Receptors

This review describes the various subtypes of gamma-aminobutyric acid (GABA) receptors found at the echinoderm neuromuscular junction (NMJ), based on pharmacological and physiological studies. The review focuses mainly on holothurian GABA receptors at the NMJ located between the radial nerve and longitudinal muscle of the body wall (LMBW) and compares them to GABA receptors described at other echinoderm NMJs. Since a primary action of GABA on the holothurian LMBW is to modulate contractile responses to the excitatory neurotransmitter, acetylcholine (ACh), the pharmacology of echinoderm nicotinic ACh receptors (nAChRs) and muscarinic ACh receptors (mAChRs) is also addressed. GABA responses have been described in the asteroids, echinoids and holothuroids but not in the other echinoderm classes. Some actions of GABA on echinoderm muscle include regulation of basal tone and spontaneous rhythmic contractions and modulation of cholinergic responses. Both GABA A and B receptor subtypes are present at the echinoderm NMJ, a feature also common to the arthropods, molluscs and chordates. Echinoderm GABA A receptors may mediate the excitatory responses to GABA. The GABA A receptor antagonist bicuculline has a paradoxical effect on contractility, stimulating large protracted contractions of the LMBW. The GABA A agonist muscimol potentiates cholinergic contractions of the holothurian LMBW. Another population of GABA receptors is inhibitory and is sensitive to the GABA B agonist baclofen and GABA B antagonists phaclofen and 2-OH-saclofen. The pre- and/or postsynaptic location of the GABA A and B receptors is not currently known. The folded GABA analogue 4-cis-aminocrotonic acid has no effect on the contractility of the holothurian LMBW so GABA C receptors are probably lacking in this preparation. Pharmacological studies have shown that distinct nAChRs and mAChRs are colocalized in numerous echinoderm muscle preparations. Most recently, nAChR agonists were used to characterize pharmacologically receptors at the holothurian LMBW that bind ACh. Nicotinic AChRs with unique pharmacological profiles are localized both pre- and postsynaptically at this NMJ, where their physiological action is to enhance muscle tone. Muscarinic agonists also have excitatory actions on the LMBW but their action is to stimulate phasic, rhythmic contractions of the muscle. The location of mAChRs at the echinoderm NMJ, however, is unknown.Since most of the studies described in the present review have used whole-mount preparations consisting largely of a combination of muscle fibers, neurons and connective tissue, it is extremely difficult to determine pharmacologically the exact location of the various receptor subtypes. Additional electrophysiological studies on isolated neurons and muscle fibers are therefore required to clearly define extra-, pre- and/or postsynaptic sites for the receptor subtypes at the echinoderm NMJ.

Regulation of endogenous dopamine release in amphibian retina by gamma-aminobutyric acid and glycine

1994 ◽  
Vol 11 (5) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jeffrey H. Boatright ◽  
Nara M. Rubim ◽  
P. Michael Iuvone
Keyword(s):  
Receptor Agonist ◽  
Dopamine Release ◽  
Receptor Activation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Endogenous Dopamine ◽  
Endogenous Dopamine Release ◽  
Inhibitory Tone

AbstractEndogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light.Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.

Nitrous Oxide-induced Enhancement of γ-Aminobutyric Acid-A-mediated Chloride Currents in Acutely Dissociated Hippocampal Neurons 

1998 ◽  
Vol 88 (2) ◽  
pp. 473-480 ◽  
Author(s):  
Misa Dzoljic ◽  
Bert Van Duijn
Keyword(s):  
Nitrous Oxide ◽  
Hippocampal Neurons ◽  
Prolonged Exposure ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Patch Clamp Recording ◽  
Gaba A ◽  
Ca1 Region ◽  
Tube Application

Background Because the synaptic inhibition in the human brain is largely mediated by gamma-aminobutyric acid (GABA), the GABA receptor is of primary interest for the study of the working mechanism of general anesthetics. This article examines the interaction between this type of ion channel and nitrous oxide (N2O). Methods Patch clamp recording techniques were applied to investigate the effects of N2O on GABA(A) receptor channels in a whole-cell configuration at room temperature. Acutely dissociated rat hippocampal cells from the CA1 region were used. Rapid application of the agonist muscimol and anesthetics (N2O, pentobarbital, and ethanol) was accomplished using a Y tube application system. Peak chloride (Cl-) currents were measured. Results Short-term application of muscimol (5-30 microM) with dissolved N2O (80%, approximately 22.5 mM) increased the Cl- current (approximately 140%) compared with muscimol alone. This effect is comparable with results the authors obtained with ethanol (800 mM) and pentobarbital (100 microM). Prolonged exposure (9 min) to N2O further increased Cl- currents by an additional 50%. Concentrations of N2O lower than 12 mM did not show an enhancement of this current, whereas application of N2O alone did not result in any Cl- conductance. Conclusions These results indicate that N2O can enhance GABA(A) channel-mediated Cl- currents by modulating the effect of the specific GABA(A) agonist; it is not active by itself.

scholarly journals Identification of channel-lining residues in the M2 membrane-spanning segment of the GABA(A) receptor alpha1 subunit.

1996 ◽  
Vol 107 (2) ◽  
pp. 195-205 ◽  
Author(s):  
M Xu ◽  
M H Akabas
Keyword(s):  
Ion Selectivity ◽  
Alpha Helix ◽  
Covalent Modification ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Charge Selectivity ◽  
Helical Wheel ◽  
Ion Conducting ◽  
Membrane Spanning

The gamma-aminobutyric acid type A (GABA(A)) receptors are the major inhibitory, postsynaptic, neurotransmitter receptors in the central nervous system. The binding of gamma-aminobutyric acid (GABA) to the GABA(A) receptors induces the opening of an anion-selective channel that remains open for tens of milliseconds before it closes. To understand how the structure of the GABA(A) receptor determines the functional properties such as ion conduction, ion selectivity and gating we sought to identify the amino acid residues that line the ion conducting channel. To accomplish this we mutated 26 consecutive residues (250-275), one at a time, in and flanking the M2 membrane-spanning segment of the rat alpha1 subunit to cysteine. We expressed the mutant alpha1 subunit with wild-type beta1 and gamma2 subunits in Xenopus oocytes. We probed the accessibility of the engineered cysteine to covalent modification by charged, sulfhydryl-specific reagents added extracellularly. We assume that among residues in membrane-spanning segments, only those lining the channel would be susceptible to modification by polar reagents and that such modification would irreversibly alter conduction through the channel. We infer that nine of the residues, alpha1 Val257, alpha1 Thr26l, alpha1 Thr262, alpha1 Leu264, alpha1 Thr265, alpha1 Thr268, alpha1 Ile27l, alpha1 Ser272 and alpha1 Asn275 are exposed in the channel. On a helical wheel plot, the exposed residues, except alpha1 Thr262, lie on one side of the helix in an arc of 120 degrees. We infer that the M2 segment forms an alpha helix that is interrupted in the region of alpha1 Thr262. The modification of residues as cytoplasmic as alpha1 Val257 in the closed state of the channel suggests that the gate is at least as cytoplasmic as alpha1 Val257. The ability of the positively charged reagent methanethiosulfonate ethylammonium to reach the level of alpha1 Thr261 suggests that the charge-selectivity filter is at least as cytoplasmic as this residue.

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