Regulatory mechanisms that govern nicotinic synapse formation in neurons

Rosenberg, Madelaine M.; Blitzblau, Rachel; Olsen, Douglas P.; Jacob, Michele H.

doi:10.1002/neu.10112

Cited by 19 publications

(14 citation statements)

References 126 publications

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“…Major heteromeric receptors are α3α5β4 or α4β2 combinations and these can function -in analogy to muscle nAChRs -as postsynaptic receptors mediating rapid cholinergic synaptic transmission. This process is prominent in autonomic ganglionic neurons [8] and target organs such as adrenal chromaffin cells [9], where α3α5β4 nAChRs mediate cholinergic input, in the latter case leading to secretion of catecholamines. In the brain, fast synaptic transmission mediated by postsynaptic nAChRs is rare [4].…”

Section: Introductionmentioning

confidence: 99%

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Wiesner

Fuhrer

2006

Cell. Mol. Life Sci.

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Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the functional consequences are different. While concerted action of MuSK, Abl- and Src-family kinases (SFKs) regulates the synaptic distribution of nAChRs at the neuromuscular junction, SFKs activate heteromeric neuronal nAChRs in adrenal chromaffin cells, thereby enhancing catecholamine secretion. In contrast, the activity of homomeric neuronal nAChRs, as found in the hippocampus, is negatively regulated by tyrosine phosphorylation and SFKs. It appears that tyrosine kinases provide the means to regulate all nAChRs; but the functional consequences, even those caused by the same kinase family, are specific for each receptor subtype and location.

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Section: Introductionmentioning

confidence: 99%

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Wiesner

Fuhrer

2006

Cell. Mol. Life Sci.

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“…Third, ␤4/␣3/␣5 transcripts are coordinately upregulated during synaptogenesis in autonomic ganglia (12,32). All three clustered genes are coordinately upregulated by presynaptic innervation, while ␤4/␣3 but not ␣5 transcript levels are upregulated by target tissue interactions (31,47). The effect of presynaptic input on ␤4/␣3/␣5 transcript levels can be mimicked by treatment of developing autonomic neurons with neuregulin isoforms (62).…”

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confidence: 99%

Shared Long-Range Regulatory Elements Coordinate Expression of a Gene Cluster Encoding Nicotinic Receptor Heteromeric Subtypes

Xiao-hong

Scott²,

Deneris³

2006

Molecular and Cellular Biology

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The nicotinic acetylcholine receptor (nAChR) ␤4/␣3/␣5 gene cluster encodes several heteromeric transmitter receptor subtypes that are essential for cholinergic synaptic transmission in adrenal gland, autonomic ganglia, pineal gland, and several nuclei in the central nervous system. However, the transcriptional mechanisms coordinating expression of these subunit genes in different cell populations are unknown. Here, we used transgenic methods to investigate long-range transcriptional control of the cluster. A 132-kb P1-derived artificial chromosome (PAC) encoding the rat cluster recapitulated the neurally-and endocrine-restricted expression patterns of the endogenous ␤4/␣3/␣5 genes. Mutation of ETS factor binding sites in an enhancer, ␤43, embedded in the ␤4 3-untranslated exon resulted in greatly diminished ␤4, ␣3, and ␣5 expression in adrenal gland and to a lesser extent in the superior cervical ganglion (SCG) but not in other tissues. Phylogenetic sequence analyses revealed several conserved noncoding regions (CNRs) upstream of ␤4 and ␣5. Deletion of one of them (CNR4) located 20 kb upstream of ␤4 resulted in a dramatic decrease in ␤4 and ␣3 expression in the pineal gland and SCG. CNR4 was sufficient to direct LacZ transgene expression to SCG neurons, which express the endogenous ␤4␣3␣5 subunits, and pineal cells, which express the endogenous ␤4␣3 combination. Finally, CNR4 was able to direct transgene expression to major sites of expression of the endogenous cluster in the brain. Together, our findings support a model in which cell type-specific shared long-range regulatory elements are required for coordinate expression of clustered nAChR genes.Recent evidence from whole-genome studies has led to the conclusion that gene clustering is common in the eukaryotic genome (8, 26). Two well-studied clusters are the ␤-globin and Hox loci, in which clustering is thought to facilitate interactions between gene-proximal elements in or near individual promoters and shared long-range regulatory elements. These interactions are necessary for correct cell type-and stage-specific switching of ␤-globin gene expression during erythropoiesis and coordinate expression of Hox genes in order for them to fulfill their roles in limb development and in patterning the main body axis (34, 52). Many gene clusters are expressed either exclusively or predominantly in the nervous system, but the mechanisms involved are not understood (19,51,67). The prevalence of eukaryotic gene clusters suggests that the identification of the transcriptional mechanisms governing their expression will be important for understanding the differentiation of specific cell types and perhaps the molecular basis of disease (29).A phylogenetically conserved cluster of nicotinic acetylcholine receptor (nAChR) subunit genes, ␤4/␣3/␣5, encodes heteromeric neurotransmitter-gated cation channels that are critically important for fast cholinergic synaptic transmission (7,11,13). Several observations indicate that the clustered genes are coordinately regulated. First, a...

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“…In the present study, the penile PG neurons were immune to BOO, suggesting that the bladder-derived retrograde signal(s) may cause altered nAChR expression in bladder PG neurons of rats with BOO. Consistent with this notion, retrograde signals from target tissues appear to be essential for maintaining nAChR levels in CNS and PNS neurons (Albuquerque et al, 2009;Rosenberg et al, 2002 As an internal reference, β-actin was amplified. To analyze fold changes in gene expression, the comparative 2 À ΔΔCT method was used.…”

Section: Discussionmentioning

confidence: 77%

Bladder outlet obstruction causes up-regulation of nicotinic acetylcholine receptors in bladder-projecting pelvic ganglion neurons

et al. 2015

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Regulatory mechanisms that govern nicotinic synapse formation in neurons

Cited by 19 publications

References 126 publications

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Shared Long-Range Regulatory Elements Coordinate Expression of a Gene Cluster Encoding Nicotinic Receptor Heteromeric Subtypes

Bladder outlet obstruction causes up-regulation of nicotinic acetylcholine receptors in bladder-projecting pelvic ganglion neurons

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