Structural and Functional Heterogeneity of Nicotinic Receptors

Lindstrom, Jon; Schoepfer, Ralf; Conroy, William G.; Whiting, Paul J.

doi:10.1002/9780470513965.ch3

Cited by 16 publications

(8 citation statements)

References 60 publications

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“…In brief, 500 μg of cell lysate was layered over streptavidin‐coated or protein G Dynabeads (Life Technologies) conjugated to biotin‐α‐Bgtx (Life Technologies), anti‐Gαq polyclonal Abs (Abcam), or purified immunoglobulin G (IgG) Ab (Cell Signaling, Danvers, MA, USA) as an immunopreciptation control. Protein complexes were separated by gel electrophoresis on a 4–12% Bis‐Tris gradient gel (Invitrogen) for Western blot analysis using the following Abs at 1 μg/ml: mAb 306 (21); Gαq, growth‐associated protein 43 (GAP‐43), IP 3 R, and pIP 3 R (Abcam); and GAPDH (Cell Signaling). Species‐specific peroxidase‐conjugated secondary Abs (Jackson ImmunoResearch) were used at a concentration of 0.4 μg/ml.…”

Section: Methodsmentioning

confidence: 99%

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway

Nordman

Kabbani

2014

FASEB j.

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The α7 nicotinic receptor (α7) plays an important role in neuronal growth and structural plasticity in the developing brain. We have recently characterized a G-protein-signaling pathway regulated by α7 that directs the growth of neurites in developing neural cells. Now we show that choline activation of α7 promotes a rise in intracellular calcium from local ER stores via Gαq signaling, leading to IP3 receptor (IP3R) activation at the growth cone of differentiating PC12 cells. A mutant α7 significantly attenuated in calcium conductance (D44A; P<0.001) was found to be unable to promote IP3R signaling and calcium store release. In addition, calcium elevation via α7 correlates with a significant attenuation in the rate of microtubule invasion of the growth cone (P<0.001). This process was also attenuated in the D44A mutant and blocked by an inhibitor of the IP3R, suggesting that calcium flow through the α7 channel and activation of the Gαq pathway are necessary for growth. Taken together, the findings reveal an inhibitory mechanism of α7 on cytoskeletal growth via the intracellular calcium activity of the receptor channel and the Gαq signaling pathway at the growth cone.-Nordman, J. C., Kabbani, N. Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP3 receptor pathway.

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Section: Methodsmentioning

confidence: 99%

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway

Nordman

Kabbani

2014

FASEB j.

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“…IP experiments were performed by first incubating membrane proteins with an anti‐α7 monoclonal Ab (mAb306; Lindstrom et al . ) or an anti‐Gprin1 rabbit polyclonal Ab (Abcam) followed by extraction using protein G Dynabeads (Invitrogen). Control IP experiments were performed by incubating the same amount of membrane proteins (MP, 100 μg) with an equal amount of a pure polyclonal rabbit IgG Ab (5 μg) (Cell Signaling Technology, Beverly, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth

Nordman

Phillips

Kodama

et al. 2014

Journal of Neurochemistry

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Cholinergic signaling plays an important role in regulating the growth and regeneration of axons in the nervous system. The α7 nicotinic receptor (α7) can drive synaptic development and plasticity in the hippocampus. Here we show that activation of α7 significantly reduces axon growth in hippocampal neurons by coupling to G protein regulated inducer of neurite outgrowth 1 (Gprin1), which targets it to the growth cone (GC). Knockdown of Gprin1 expression using RNAi is found sufficient to abolish the localization and calcium signaling of α7 at the GC. In particular, α7/Gprin1 interaction appears intimately linked to a Gαo, GAP-43, and CDC42 cytoskeletal regulatory pathway within the developing axon. These findings demonstrate that α7 regulates axon growth in hippocampal neurons, thereby likely contributing to synaptic formation in the developing brain.

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“…The importance of nAChRs in the human brain is now well established and appreciated as indicated by several excellent reviews on their molecular and functional structure [97, 117, 118], anatomical distribution [119, 120], physiology [121], as well as therapeutic indication for the treatment of several diseases such as Alzheimer’s disease, schizophrenia, epilepsy, pain, Parkinson’s disease, and nicotine and alcohol dependence [122–125]. …”

Section: Neuronal Nicotinic Acetylcholine Receptors: a Common Biologimentioning

confidence: 99%

Neuronal Nicotinic Acetylcholine Receptors as Pharmacotherapeutic Targets for the Treatment of Alcohol Use Disorders

Chatterjee

Bartlett²

2010

CNSNDDT

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Alcohol use disorders (AUDs) are complex and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinical data provide evidence that nicotine administration increases alcohol intake and non-specific nicotinic receptor antagonists reduce alcohol-mediated behaviors. As nicotine interacts specifically with the neuronal nicotinic acetylcholine receptor (nAChR) system, this suggests that nAChRs play an important role in the behavioral effects of alcohol. In this review, we discuss the importance of nAChRs for the treatment of AUDs and argue that the use of FDA approved nAChR ligands, such as varenicline and mecamylamine, approved as smoking cessation aids may prove to be valuable treatments for AUDs. We also address the importance of combining effective medications with behavioral therapy for the treatment of alcohol dependent individuals.

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Structural and Functional Heterogeneity of Nicotinic Receptors

Cited by 16 publications

References 60 publications

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway

Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth

Neuronal Nicotinic Acetylcholine Receptors as Pharmacotherapeutic Targets for the Treatment of Alcohol Use Disorders

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Structural and Functional Heterogeneity of Nicotinic Receptors

Cited by 16 publications

References 60 publications

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP3receptor pathway

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP3receptor pathway

Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth

Neuronal Nicotinic Acetylcholine Receptors as Pharmacotherapeutic Targets for the Treatment of Alcohol Use Disorders

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Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway

Microtubule dynamics at the growth cone are mediated by α7 nicotinic receptor activation of a Gαq and IP₃receptor pathway