scholarly journals Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

2008 ◽  
Vol 181 (3) ◽  
pp. 511-521 ◽  
Author(s):  
Melissa L. Hancock ◽  
Sarah E. Canetta ◽  
Lorna W. Role ◽  
David A. Talmage
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Surface Expression ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Phosphatidylinositol 3 Kinase ◽  
Nicotinic Acetylcholine ◽  
Type Iii ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Erbb Signaling ◽  
Α7 Nachrs

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

2021 ◽  
Author(s):  
Zilin Li ◽  
Chenyu Gou ◽  
Wenhui Wang ◽  
Yuan Li ◽  
Yu Cui ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Hippocampal Neurons ◽  
Acetylcholine Receptors ◽  
Pdz Domain ◽  
Surface Expression ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Downstream Signaling ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Cultured Hippocampal Neurons

Abstract α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are expressed widely in the brain, where they contribute to a variety of behaviors including arousal and cognition, participate in a number of neurodegenerative disorders including Alzheimer’s and Parkinson’s disease, and is responsible for nicotine addiction. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated are still less well understood. Here we show that the regulation of the α7nAChRs is controlled by PDLIM5 in the endogenous PDZ domain proteins family. We find that chronic exposure to 1 μM nicotine up-regulated both α7, β2-contained nAChRs and PDLIM5 in primary cultured hippocampal neurons, and the up-regulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, the α7nAChRs and β2nAChRs display distinct patterns of expression, with α7 co-localized more with PDLIM5. Meanwhile, PDLIM5 interacts with native brain α7 but not β2 nAChRs in neurons. Moreover, knocking down of PDLIM5 in heterologous cells abolishes nicotine-induced up-regulation of α7nAChRs. In cultured hippocampal neurons, shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs mediated currents. Proteomics analysis shows PDLIM5 interacts with α7nAChRs through the PDZ domain and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in regulating α7nAChRs, which may be relevant to plastic changes in the nervous system.

Presynaptic type III neuregulin1-ErbB signaling targetsα7 nicotinic acetylcholine receptors to axons

2008 ◽  
Vol 131 (6) ◽  
pp. i4-i4 ◽  
Author(s):  
Melissa L. Hancock ◽  
Sarah E. Canetta ◽  
Lorna W. Role ◽  
David A. Talmage
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Type Iii ◽  
Erbb Signaling

scholarly journals Procognitive effects of varenicline in the animal model of schizophrenia depend on α4β2- and α7-nicotinic acetylcholine receptors

2018 ◽  
Vol 33 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Agnieszka Potasiewicz ◽  
Joanna Golebiowska ◽  
Piotr Popik ◽  
Agnieszka Nikiforuk
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Partial Agonist ◽  
Set Shifting ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Α7 Nachrs

Background: Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR), is currently used to facilitate smoking cessation. Preclinical and clinical studies have suggested that this compound may also be effective in treating cognitive impairments in schizophrenia. However, it is unclear which nicotinic acetylcholine receptor subtypes may be involved because varenicline is not only a partial agonist for α4β2-nAChRs but also a full agonist for α7 nicotinic acetylcholine receptors (α7-nAChRs). Aim: We investigated the effects of varenicline, compared to the α4β2-nAChR partial agonist TC-2403 and the α7-nAChR full agonist PNU-282987, in a ketamine-based model of schizophrenia-like cognitive deficits on the attentional set-shifting task in rats. The second goal was to elucidate whether the procognitive efficacy of varenicline was due to the compound’s action on α4β2-nAChRs or α7-nAChRs. Methods: Ketamine was administered to rats for 10 consecutive days and the test was performed 14 days following the last injection. The tested compounds were administered 30 min prior to the attentional set-shifting task. Results: Varenicline, TC-2403 and PNU-282987 ameliorated ketamine-evoked set-shifting deficits. While the α4β2-nAChR antagonist dihydro-β-erythroidine and the α7-nAChR antagonist methyllycaconitine completely prevented the procognitive actions of TC-2403 and PNU-282987, respectively, varenicline’s effect was only partially blocked by any given antagonist. Moreover, the combined treatment with TC-2403 and PNU-282987 more effectively facilitated rats’ set-shifting ability than activation of either type of nicotinic acetylcholine receptor alone. Conclusion: The present findings demonstrated that varenicline’s actions on both α7-nAChRs and α4β2-nAChRs may be necessary to produce its full procognitive effect in the present experimental setting.

scholarly journals Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7251
Author(s):  
Petrilla Jayaprakash ◽  
Dmytro Isaev ◽  
Waheed Shabbir ◽  
Dietrich E. Lorke ◽  
Bassem Sadek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Pathological Condition ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Nicotinic Acetylcholine ◽  
Oxidative Stress Status ◽  
Inward Currents ◽  
Α7 Nachrs

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

scholarly journals Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 164
Author(s):  
Lina Son ◽  
Elena Kryukova ◽  
Rustam Ziganshin ◽  
Tatyana Andreeva ◽  
Denis Kudryavtsev ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Central Loop ◽  
Acetylcholine Binding Proteins ◽  
Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

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