Molecular underpinnings of neuronal nicotinic acetylcholine receptor expression

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are critical signaling molecules in a broad variety of fundamental biological processes. In order for cholinergic signaling to function normally, the receptors must be expressed in the appropriate cells at the appropriate times. Expression of the receptors is regulated at many levels from transcription of the receptor subunit genes to posttranslational modifi cations of individual subunits. Regulating nAChR expression is further complicated because of the large number of genes encoding nAChR subunits, most of which, but not all, are located on distinct chromosomes. Here, we describe molecular events that underlie expression of nAChR subunit genes. We begin with a survey of the transcriptional mechanisms involved in nAChR subunit gene expression including a review of CHRNA5/A3/B4 cluster expression. An update on two emerging fields of investigation, microRNA and epigenetic regulation of nAChR expression, is provided followed by an overview of mechanisms involved in the nicotine-mediated upregulation of nAChR expression. Regulation of nAChR subunit expression is of fundamental importance as it underlies subunit availability, which impacts individual receptor subtype composition and thus, the biophysical properties of the nAChRs.