scholarly journals Nicotinic Acetylcholine Receptors as Targets for Tobacco Cessation Therapeutics: Cutting-Edge Methodologies to Understand Receptor Assembly and Trafficking

2016 ◽  
pp. 119-132 ◽  
Author(s):  
Ashley M. Fox-Loe ◽  
Linda P. Dwoskin ◽  
Christopher I. Richards
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Tobacco Cessation ◽  
Cutting Edge ◽  
Nicotinic Acetylcholine ◽  
Receptor Assembly

scholarly journals Concatenated nicotinic acetylcholine receptors: A gift or a curse?

2018 ◽  
Vol 150 (3) ◽  
pp. 453-473 ◽  
Author(s):  
Philip Kiær Ahring ◽  
Vivian Wan Yu Liao ◽  
Thomas Balle
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Three Dimensional ◽  
Mammalian Brain ◽  
Nicotinic Acetylcholine ◽  
Novel Treatments ◽  
Full Control ◽  
Ion Conducting ◽  
Receptor Assembly ◽  
Receptor Family

Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are vital for normal mammalian brain function. Cys-loop receptors are pentameric ligand-gated ion channels formed from five identical or homologous subunits oriented around a central ion-conducting pore, which result in homomeric or heteromeric receptors, respectively. Within a given Cys-loop receptor family, many different heteromeric receptors can assemble from a common set of subunits, and understanding the properties of these heteromeric receptors is crucial for the continuing quest to generate novel treatments for human diseases. Yet this complexity also presents a hindrance for studying Cys-loop receptors in heterologous expression systems, where full control of the receptor stoichiometry and assembly is required. Therefore, subunit concatenation technology is commonly used to control receptor assembly. In theory, this methodology should facilitate full control of the stoichiometry. In reality, however, we find that commonly used constructs do not yield the expected receptor stoichiometries. With ternary or more complex receptors, concatenated subunits must assemble uniformly in only one orientation; otherwise, the resulting receptor pool will consist of receptors with mixed stoichiometries. We find that typically used constructs of α4β2 nAChR dimers, tetramers, and pentamers assemble readily in both the clockwise and the counterclockwise orientations. Consequently, we investigate the possibility of successfully directing the receptor assembly process using concatenation. We begin by investigating the three-dimensional structures of the α4β2 nAChR. Based on this, we hypothesize that the minimum linker length required to bridge the C terminus of one subunit to the N terminus of the next is shortest in the counterclockwise orientation. We then successfully express receptors with a uniform stoichiometry by systematically shortening linker lengths, proving the hypothesis correct. Our results will significantly aid future studies of heteromeric Cys-loop receptors and enable clarification of the current contradictions in the literature.

Nicotinic acetylcholine receptors in the patients with Parkinson's disease: 5IA-SPECT

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S586-S586 ◽  
Author(s):  
Kazuo Hashikawa ◽  
Hidefumi Yoshida ◽  
Nobukatsu Sawamoto ◽  
Shigetoshi Takaya ◽  
Chihiro Namiki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine
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