Chromosomal localization and physical linkage of the genes encoding the human α3, α5, and β4 neuronal nicotinic receptor subunits

Raimondi, Elena; Rubboli, Francesca; Moralli, Daniela; Chini, Bice; Fornasari, Diego; Tarroni, Paola; Carli, L. De; Clementi, Francesco

doi:10.1016/0888-7543(92)90324-l

Cited by 41 publications

(22 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One level at which nAChR expression can be regulated is the transcriptional control of the subunit genes. The ␤4, ␣3, and ␣5 subunit genes form a unique gene cluster in mammals and birds Couturier et al, 1990;Raimondi et al, 1992). This cluster is organized with ␤4 being most 5Ј, followed by ␣3 and ␣5; ␣5 is transcribed in the opposite direction from ␤4 and ␣3.…”

Section: Molecular Mechanisms That Regulate Neuronal Nachr Expressionmentioning

confidence: 99%

Regulatory mechanisms that govern nicotinic synapse formation in neurons

et al. 2002

View full text Add to dashboard Cite

Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

show abstract

Section: Molecular Mechanisms That Regulate Neuronal Nachr Expressionmentioning

confidence: 99%

Regulatory mechanisms that govern nicotinic synapse formation in neurons

et al. 2002

View full text Add to dashboard Cite

show abstract

“…1A). The 4.3 KN construct containing the whole intergenic region between ␤4 and ␣3 (13,14,22) was stimulated by ϳ3-fold (Fig. 1B), to the same extent as the 4xTK plasmid (Fig.…”

Section: Transcriptional Effects Of Phox2a On the Activity Of The ␣3mentioning

confidence: 99%

Transcription Factor PHOX2A Regulates the Human α3 Nicotinic Receptor Subunit Gene Promoter

Benfante

Flora

Lascio

et al. 2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

PHOX2A is a paired-like homeodomain transcription factor that participates in specifying the autonomic nervous system. It is also involved in the transcriptional control of the noradrenergic neurotransmitter phenotype as it regulates the gene expression of tyrosine hydroxylase and dopamine-␤-hydroxylase. The results of this study show that the human orthologue of PHOX2A is also capable of regulating the transcription of the human ␣3 nicotinic acetylcholine receptor gene, which encodes the ligand-binding subunit of the ganglionic type nicotinic receptor. In particular, we demonstrated by chromatin immunoprecipitation and DNA pulldown assays that PHOX2A assembles on the SacI-NcoI region of ␣3 promoter and, by cotransfection experiments, that it exerts its transcriptional effects by acting through the 60-bp minimal promoter. PHOX2A does not seem to bind to DNA directly, and its DNA binding domain seems to be partially dispensable for the regulation of ␣3 gene transcription. However, as suggested by the findings of our co-immunoprecipitation assays, it may establish direct or indirect protein-protein interactions with Sp1, thus regulating the expression of ␣3 through a DNA-independent mechanism. As the ␣3 subunit is expressed in every terminally differentiated ganglionic cell, this is the first example of a "pan-autonomic" gene whose expression is regulated by PHOX2 proteins.The high degree of cellular heterogeneity of the mammalian nervous system is because of distinct specification and differentiation processes that mainly rely on transcriptional control mechanisms mediated by transcription factors having discrete temporal patterns of region-specific and cell type-specific expression.PHOX2A and PHOX2B are paired-like homeodomain proteins that have been shown to play a pivotal role in the development of the three peripheral divisions of the autonomic nervous system (1). They are also expressed in all of the noradrenergic neurons of the brainstem, in some cranial sensory ganglia that participate in autonomic reflexes, and in a subset of cranial motor neurons (2). None of the components of the autonomic nervous system develop properly in Phox2b knock-out mice (3), whereas Phox2a null mutants show an apparently less severe phenotype that only involves the agenesis of the Locus coeruleus and atrophy of the cranial sensory ganglia (4); nevertheless, they do not feed and die on the day of birth. The different phenotypes of Phox2 knock-out mutants along with their asynchronous onset of expression during development underscore that the two factors are not functionally equivalent. This has been more directly demonstrated by reciprocal gene replacement experiments (5) that led to the conclusion that biochemical differences may be responsible for the specific function of each paralogue.It is worth noting that PHOX2 proteins are also involved in the transcriptional control of the neurotransmitter phenotype (6); they play a fundamental role in the terminal differentiation of the orthosympathetic system as they regulate the gene...

show abstract

“…32 KIRSTEIN AND INSEL are clustered on chromosome 15q24, and until recently, the gene structures (i.e., exact genomic size and exonintron boundaries) and the organization of the gene cluster were unknown, making comprehensive mutational analysis difficult (Weiland et al, 2000;Duga et al, 2001). The three genes in the cluster are physically linked (Raimondi et al, 1992), and the genes for the ␣3 and ␣5 subunits partially overlap at their 3Ј ends (Duga et al, 2001). The genes in the cluster have been reported to be coexpressed, and regulatory elements that influence transcription of both the ␣3 and ␤4 genes have been identified (Deneris et al, 2000).…”

Section: A Nicotinic Cholinergic Receptorsmentioning

confidence: 99%