Cell specificity of a rat neuronal nicotinic acetylcholine receptor alpha7 subunit gene promoter.

摘要

Neuronal nAChRs are pentameric transmembrane proteins which function as ligand-gated ion channels and are composed of multiple alpha and beta subunits. Nine neuronal nAChR alpha subunit genes (alpha2-alpha10) and three nAChR beta subunit genes (beta2-beta4) have been identified. nAChR subtypes are heteromers, composed of various combinations of nAChR subunits or homomers composed of alpha7, alpha8, or alpha9 subunits. nAChR subtypes are widely expressed in the nervous system, yet each subunit has a distinct and unique pattern of expression. This report focuses on the expression of the nAChR alpha7 gene since homomeric nAChRs can be formed from this one subunit, simplifying a study of the expression of a specific nAChR subtype. Alpha7 nAChRs are involved in several important biological activities in addition to synaptic transmission including mediating neurite outgrowth, neuronal development and cell death, and in presynaptic control of neurotransmitter release. Transcriptional regulation of alpha7 gene expression may be important to control the location and timing of these events. We previously isolated a rat alpha7 nAChR promoter and studied expression in PC12 cells. In this study we examined the expression of the alpha7 promoter in PC12, HEK293, L6, SN17 and Neuro-2A cells in order to define elements necessary for cell-specific expression. Elements promoting expression of alpha7 in muscle and fibroblasts were identified. We also demonstrated that several other nAChR genes are also expressed in SN 17 and Neuro-2A cells, supporting use of these cell lines as models to study transcriptional control of nAChR genes.